We reviewed the effectiveness of commercial serological markers for the early detection of cancer and monitoring cancer patients. Parameters, such as specificity and variability of tumor markers were compared with a new approach for cancer detection which was recently developed in our laboratory. We demonstrate that the absence of tumor specificity and the extremely high variability of tumor markers are the reason that none of them can be used for early cancer diagnosis. We developed a method for the isolation of tumor-associated antigens (TAA) and found that two soluble low-molecular mass 66 and 51 kDa proteins could be isolated from the blood of cancer patients. The first protein, albumin, belongs to a group of heat-shock proteins (HSP), while the second is connected with TAA. The progress in cancer is characterized by a relative decrease in the concentration of HSP and a high increase in blood levels of TAA. Our method was shown to be highly sensitive and specific for the early detection of different types of cancer, such as of the colon, uterus, ovary, and breast, as well as melanoma.