In an attempt to investigate the neoplastic progression in different stages of actinic keratosis (AK), a standardized AgNOR analysis was performed in 94 cases of AK, 35 of which were associated with squamous cell carcinoma (SCC) or basal cell carcinoma (BCC), and in 31 cases of SCC and 22 cases of BCC. The cases were subdivided into low- and high-AgNOR-expressing (AgNOR status) AK by using the mean area of AgNORs per cell (NORA) value (3.996 micro(2)) as the cut-off. In AK samples, a progressive increase of the mean NORA value from Stage I to Stage IV was encountered. In addition, a significantly higher mean NORA value was found in the AK cases associated with SCC, in comparison to those without SCC; by contrast, no significant differences in the mean NORA value were noted between AK cases with or without BCC. A highly significant association between a high AgNOR quantity and the coexistence of SCC was encountered in AK; no association was appreciable between the AgNOR quantity and the co-occurrence of BCC. Moreover, when the co-existence of SCC in AK was considered as the reference point, the AK cases associated with SCC mostly (95.5%) presented a high AgNOR quantity (high sensitivity), but only 57.6% of cases without SCC displayed a low AgNOR quantity (low specificity). Additionally, our data document that the standardised AgNOR analysis represents a strong negative predictor for the association between SCC and AK. Indeed, a low AgNOR quantity mostly is associated with AK cases without SCC.