The current disclosure provides for methods of identifying and treating small cell neuroendocrine (SCN) tumors and small-round-blue cell tumor (SRBCT). Aspects of the disclosure relate to a method comprising measuring the level of expression of one or more biomarkers from Tables 1-3 in a biological sample from a cancer patient. Further aspects relate to a method for treating small cell neuroendocrine (SCN) cancer or small-round-blue cell tumor (SRBCT) in a patient comprising administering a cancer treatment to the patient, wherein the cancer treatment is a treatment selected from Table 4A, 4B, or combinations of treatments from Table 4A and/or 4B.