We have previously shown that a short course of recombinant interferon-alpha-2b (rIFN-alpha-2b) (3 million units day for 5 days) for patients with primary gynaecologic malignancies was able to increase the circulating levels of a newly discovered tumour associated antigen, termed 90K. In this study, we have investigated the effects of the same modality of administration of rIFN-alpha-2b in 62 patients with breast and colorectal cancer whose primary tumour was surgically removed 1 month before and who were without evidence of disease (NED) at the time of the study. A significant increase of 90K serum concentration was already observed 24 h after the first r-IFN-alpha-2b injection and persisted throughout the investigational period. The increase was more pronounced in patients with a basal 90K-negative than a 90K-positive assay. Of 54 patients who started the test with a 90K negative assay, 17 (31%) shifted to a positive assay after rIFN-alpha-2b. Twenty-eight of 62 (45%) patients exhibited a 90K value above the mean increment of the whole population. The serum levels of CEA, CA-15-3, CA 19-9, and alpha-fetoprotein measured in the same serum samples were not modified. After 2 years of follow-up, ten patients relapsed. Six of them showed a 90K increase above the mean increment of the whole population. As with ovarian cancer, the increase of 90K following r-IFN-alpha-2b administration might be of importance for the early detection of disease recurrence in clinically NED breast and colon cancer patients.