It has been previously noted that the hypoxanthine‐guanine phosphoribosyltransferase (HPRT) mutant frequency of Russian subjects is significantly higher than age‐matched Western counterparts. To further explore this difference, approximately 100 mutants collected from Russian twins reported in a previous study have been sequenced and compared to an aged‐matched Western mutant dataset. The mutational spectrum of the Russian subjects was significantly different (Adams and Skopek Monte Carlo test, P = 0.004). Curiously, this younger Russian spectrum resembles that recovered from older individuals in the West. Specifically, A:T→C:G transversions are significantly over‐represented (Fisher's Exact test, P = 0.003) in the twin spectrum as compared to the young (age ≤ 35) Western spectrum. Even more noteworthy is the observation that 42% (23/55) of the base substitutions, almost double the expected value, have not been previously reported. These observations lead to the conclusion that this group of young Russian subjects has a mutational pattern which is distinct from the pattern of mutation observed in Western counterparts. The origin of this difference, whether related to genotoxic challenge, repair, or avoidance, cannot be distinguished, but diet and other lifestyle factors clearly may be responsible. Hum Mutat 15:439–446, 2000. © 2000 Wiley‐Liss, Inc.