Alteration of the p53 tumor-suppressor gene was studied in non-Hodgkin's lymphomas (NHLs) from HIV-1-infected patients. p53 protein was over-expressed in 10 out of the 45 (22%) cases analyzed, mainly clustering in the small-non-cleaved-cell (SNC) (5/19) and Ki-1+ anaplastic large-cell (ALC) (3/8) sub-types, according to previous findings on HIV-1-unrelated NHLs. p53-positive small-non-cleaved-cell lymphomas presented a diffuse or clustered pattern of p53-positive neoplastic cells consequent upon p53-gene mutations. In contrast, in Ki-1+ ALC lymphomas p53 immunohistochemical reactivity was limited to scattered tumor cells, and no p53-gene alterations could be detected. These results suggest that p53-gene alterations play a role in the lymphomagenetic process of a fraction of HIV-1-related SNC NHLs, however with a frequency no different from that observed in HIV-1-unrelated NHLs of the same sub-type. In HIV-1-related Ki-1+ ALC lymphomas, mechanisms different from gene alterations might be implicated in over-expression of p53 protein.