The proliferative activity of four malignant cellular blue nevi (MCBN) was assessed in routinely fixed, paraffin-embedded material using staining for the argyrophilic nucleolar organizer regions (AgNORs), immunohistochemical staining for proliferating cell nuclear antigen (PCNA [PC10]), and DNA flow cytometry. The objective was to determine whether the evaluation of proliferative activity could represent a useful diagnostic parameter. Four cellular blue nevi (CBN), 10 melanocytic nevi (MN), four common blue nevi (BN), and 10 conventional malignant melanomas (MMs) were selected as controls. In the MCBN the mean AgNOR number, evaluated on the basis of 100 tumor cells, was 8.33 +/- 0.83; NORs were small and dispersed throughout the nucleus; the mean PCNA score was 31.93% +/- 4.4; and two of the cases were aneuploid and two diploid. In the CBN the AgNOR count was 3.69 +/- 0.56; NORs were large and mainly grouped in a central cluster; the mean PCNA score was 3.53% +/- 1.28; and three of the cases were diploid and one aneuploid. The AgNOR counts in the MCBN were significantly different from those in the CBN (P = .0002), MN (3.04; P = .00001), and BN (2.93; P = .00006), whereas they were not significantly different from those in the conventional MMs (7.64; P = .58). The PCNA (PC10) scores in the MCBN were significantly different from those in the CBN (P = .00003), MN (2.05%; P = .00001), and BN (5.06%; P = .00002), whereas they were not significantly different from those in the conventional MMs (28.9%; P = .49). In all the cases a linear relationship between AgNOR counts and PCNA scores was observed (r = .94, P = .00001). Our results indicate that AgNOR analysis and PCNA immunostaining can be regarded as useful additional parameters for the diagnosis of MCBN.