We currently have at hand validated cancer biomarkers that can reasonably distinguish between cancer and non-cancer patients. For example, PSA can be used as a biomarker for a group of patients without cancer (PSA histologically confirmed prostate cancer and PSA > 10 µg/liter. Because free PSA and complexed PSA have molecular masses of 30 kDa and 100 kDa, respectively, these masses are well within the current capabilities of mass spectrometers (43). Validation of this technology will be highly enhanced if it is shown that one of the discriminatory peaks identified in prostate cancer is PSA and its subfractions. The same comment applies for other validated cancer biomarkers. Surprisingly, in none of the published studies with breast, prostate, or ovarian carcinoma have the classical cancer biomarkers been identified. I believe that the inability to identify these classical cancer biomarkers is due to the low sensitivity of the SELDI-TOF approach. Until validated serum internal controls are used with this technology, the results obtained, and the sensitivity of the method, should remain in question.