The clinical significance of plasma cell acid phosphatase (PCAP) was evaluated in 143 patients with monoclonal gammapathies, using a semiquantitative cytological scoring method. Significantly higher PCAP scores were measured in overt myelomas than in MGUS or in smouldering myelomas, during the phases of activity (diagnosis, progression, relapse), and in patients with extended disease. Among various clinical and laboratory parameters, PCAP was significantly related to the percentage of bone marrow plasma cells, the neoplastic growth fraction, as determined by Ki67 monoclonal antibody, and to serum levels of C-reactive protein. An inverse relationship was also found between PCAP and hemoglobin levels. Although the patients with "flaming" plasma cells exhibited low PCAP scores and poor prognosis, on the whole, myeloma patients with PCAP scores < 200 showed a significantly longer median overall survival than those with PCAP > 200 (46 vs 20 months, p < 0.003). However, in the multivariate analysis, beta 2-microglobulin, growth fraction, performance status, and serum levels of thymidine kinase and C-reactive protein, but not PCAP, maintained a significant prognostic relevance. In conclusion, although PCAP may be considered a marker of disease activity, other parameters provide better prognostic information in myeloma patients.