Proteome analysis led to the identification and characterization of tumor‐associated protein variants by two‐dimensional electrophoresis and mass spectrometry. We focused on comparing the influence of genotoxic nitroso compounds N‐methyl‐N‐nitrosourea, diethylnitrosamine and N‐nitrosomorpholine and the nongenotoxic peroxisome proliferator Nafenopin as tumor‐inducing agents on the protein pattern of rat hepatomas. We found several tumor‐associated variants that represent members of the aldo‐keto reductase superfamily. Their induction and/or inhibition was specifically related to the carcinogen used for tumor induction. The most prominent tumor‐associated protein, rat aldose reductase‐like protein‐1 (rARLP‐1) (69% sequence identity to lens aldose reductase) and three additional types of rARLP‐1 were detected in nitroso compound‐induced rat hepatomas, while rat aldo‐keto reductase protein‐c (Rak‐c), a novel tumor‐associated variant (65% sequence identity with 3α‐hydroxysteroid dehydrogenase) was discovered in N‐methyl‐N‐nitrosourea‐induced hepatomas only. 3α‐Hydroxysteroid dehydrogenase and γ4‐3‐ketosteroid‐5β‐reductase, both liver‐specific enzymes, were reduced in amount in all hepatomas investigated, independent of their mode of induction. We conclude, that detoxification enzymes like 3α‐hydroxysteroid dehydrogenase (3α‐HSD) and γ4‐3‐ketosteroid‐5β‐reductase (5β‐Red) might be replaced in hepatomas by tumor‐associated proteins that are often present in the embryonal state, like the rARLPs or the Rak‐c protein. Their induction appears to reflect an altered constitutive pattern of detoxification enzymes, detoxifying toxic aldehydes being induced by nitroso compounds. In contrast, members of the aldo‐keto reductase superfamily have not been found in Nafenopin‐induced hepatomas. The pattern of tumor‐associated protein variants is apparently characteristic for a given group of initiating carcinogens. The hypothesis is proposed that carcinogens leave specific fingerprints at the proteome level of manifest liver tumors.