The serum prostate specific antigen (PSA), having been a valid marker for prostate cancer in 2 patients at the time of their diagnosis, ultimately became undetectable (<0.1 ng/ml) despite evidence of disease progression. This was documented by isotope bone scans and the results of subsequent CT guided bone biopsies. In both biopsy specimens, immunohistochemical staining for PSA was negative, but positive for prostate acid phosphatase after microwave antigen enhancement. In both cases the serum prostate acid phosphatase (PAP) had remained within normal limits. We would caution that prostate cancer may recur and progress with an undetectable serum PSA after antiandrogen therapy.