Photodynamic therapy (PDT) is used to treat malignant and nonmalignant diseases. It is also used for cosmetological skin treatment. PDT is generally considered to have a low risk of carcinogenicity. However, instances of nonmalignant human tumors turning malignant have been linked to PDT. In this study, we used 5-aminolevulinic (ALA) acid and 3 water soluble photosensitizers-PP(Arg)(2), PP(Ser)(2)Arg(2), PP(Ala)(2)Arg(2), all diamino acid derivatives of protoporphyrin IX-to treat benign papillomas in FVB/N mice induced by 7,12-dimethylbenz(a)anthracene (DMBA)-12-O-tetradecanoyl-phorbol-13-acetate (TPA). Of these drugs, ALA and PP(Arg)(2) were found the most efficient. PDT reduced the number of papillomas, but with increasing effectiveness of the drugs, the risk of malignant transformation of the papillomas into squamous cell carcinomas increased. The underlying mechanisms are not clear and further investigations are needed.