Efficient recognition and repair of DNA damage is essential for maintaining genomic integrity. Tissues and cell types within tissues appear to vary in both DNA damage susceptibilities and cancer incidences, yet the molecular mechanisms underlying these differences are not well understood. The purpose of this study was to characterize the baseline transcription profiles of selected genes involved in DNA damage recognition and repair processes among several tissues of healthy adult B6C3F1 mice (testis, brain, liver, spleen and heart), which are routinely used by the National Toxicology Program (NTP) to conduct long-term chemical carcinogenicity studies. Stress response, damage control and DNA repair-associated genes were differentially expressed among the tissues examined. Overall, stress response genes exhibited the greatest variation among tissues with the highest expression in liver and heart while DNA repair genes exhibited the least variation. Damage control genes associated with cell cycle regulation and DNA repair genes generally had the highest expression in testis. The expression levels of several genes were rank correlated with the spontaneous cancer incidences among these tissues. Variations in basal expression of DNA damage recognition and repair-associated genes among healthy tissues may contribute to their differential response to genotoxic agents and susceptibility to genetic disease.