Imaging does not confirm the diagnosis of tumor and nothing can replace a lesion site biopsy for histological diagnosis. Further molecular pathology classification, imaging examinations staging, tumor grading. Often, friends from China send CT scans, saying that they have diagnosed cancer and asking for treatment advice. Some friends would also ask for details of chemotherapy or targeted therapy. Each time is full of anxiety and each time is a hundred thousand times urgent. As an oncologist, instead of answering immediately, I would ask a series of questions back, asking and even questioning the diagnosis of cancer. Because we all know the tremendous impact that a cancer diagnosis and the ensuing treatment can have on patients and families, it is all the more important to be cautious and thorough and to do all kinds of tests to rule out the possibility of misdiagnosis. Before we can talk about treatment, we must first confirm the diagnosis. Therefore, I would like to talk to you here about the most basic concepts of cancer diagnosis. First, whether there is a tissue biopsy and what is the primary cancer. Cancer is basically not a diagnosis that can be made by one image. Of course, a patient’s medical history, clinical manifestations, laboratory results, etc. will help. However, nothing can replace the tissue biopsy of the lesion. With the tissue, it is possible to determine whether it is cancer or not and what kind of cancer it is based on pathological examination. For example, a CT scan may mention multiple nodular lesions in the liver, and some reports will say it is liver cancer. However, liver is one of the most common organs for metastasis of many types of cancer. For example, colorectal cancer, breast cancer, and so on. It is important not to confuse primary cancer with metastatic cancer. Because the treatment plan will be very different and the prognosis is also very different. Similarly, since many cancers tend to metastasize to the lung, liver, bone, adrenal gland, lymph nodes, and brain, etc., it is important not to make arbitrary conclusions about the lesions seen in these areas. The diagnosis can only be confirmed after a pathological analysis of the tissues obtained through needling or surgery. With the progress of medical research, our understanding of each type of cancer has become more and more advanced and the classification has become more and more detailed. For example, lung cancer used to be classified into only two categories, small cell and non-small cell. But in the non-small cell category, there are now adenocarcinoma, squamous carcinoma, large cell neuroendocrine carcinoma, and so on. These careful distinctions allow us to understand the different responses in treatment, which in turn leads to new and more targeted therapies. More importantly, molecular pathology can screen for genetic mutations and determine which patients can be treated with targeted drugs. But these are usually detected only with a tissue biopsy. If targeted therapies are administered without even a biopsy or without checking for mutations, it is not only a waste of money but also a waste of precious time to treat patients who are more than half without mutations. In contrast, isn’t it necessary to spend some time to do homework during the initial diagnosis in order to prescribe the right medicine? Second, cancer staging. This is usually understood by everyone. The stage of cancer determines the prognosis, survival, and specific treatment. This is usually confirmed by imaging. PET and CT scans are commonly used. Early stage cancers can usually be treated with surgery and radiotherapy. Once it has spread, advanced cancers can only be treated with chemotherapy (there are exceptions). If the initial scan suggests a primary cancer site, for example, a lobar lung lesion with spread to lymph nodes or pleural effusion, then a lymph node biopsy or pleural fluid aspiration can not only confirm the cancer in situ, but can also help on a regular basis. Here again, the importance of tissue biopsy is emphasized. For the targeted therapy that everyone is concerned about, it should be understood that lung cancer is only applicable to the corresponding targeted therapy drugs if it is advanced with relevant genetic mutations. In the case of early stage lung cancer, whether and when to apply targeted therapies are still in the clinical trial stage. Therefore, treatment should still be carried out according to conventional surgery, or radiotherapy. The importance of cancer staging is very clear here. Thirdly, the grading of cancer. This concept refers to the degree of malignancy of cancer. If a tissue biopsy is done, the report may mention hypofractionated, moderately differentiated, or highly differentiated cancer. The lower the degree of differentiation, the more malignant the cancer is, the more likely it is to spread, and recur, the higher the grade. The grading of cancer itself is usually not a determinant of treatment, but has a very important adjunctive significance. Depending on the patient’s physical condition, the cancer grade may help the doctor and patient decide on the intensity and duration of the treatment plan. Occasionally, inert tumors such as follicular lymphoma with high grade may be treated more similarly to malignant diffuse large B lymphoma. In conclusion, the above three points are fundamental to the diagnosis of solid tumors. Here is a case. I have a patient who had early breast cancer seven years ago and recovered very well after treatment. During the routine review, she was found to have enlarged lymph nodes in the neck. A CT scan revealed a four centimeter sized lung lesion and enlarged mediastinal lymph nodes. There were also multiple bone metastases. A lymph node biopsy of the neck was easily performed and was quickly confirmed to be metastatic lung adenocarcinoma. The patient was diagnosed with advanced lung cancer and received first-line standardized combination chemotherapy before being switched to single-drug maintenance therapy. Her lung cancer and lymph nodes all disappeared. However, about six months later there were new multiple metastases to the liver. And persistent very atypical severe allogeneic cytopenia. A bone marrow aspiration surprised us to find that the bone metastases were not lung cancer, but the same breast cancer as seven or eight years earlier! Her treatment was promptly adjusted. We chose a combination chemotherapy that was equally effective for breast cancer and lung cancer. Her blood picture started to rebound and her tumor markers finally shifted to normal. This shows how important an accurate diagnosis is. So, when cancer is suspected at first diagnosis, and the progression of the disease is hard to explain, stop for a moment and see what else is possible, and what diagnostic tests can be done? Maybe you will have new findings, new treatment options and new hope.