Egypt has an unusually high proportion of early-onset colorectal cancer under age 40 years. Environmental exposures and low DNA repair capacity are among the risk factors. Because GSTM1 and GSTT1 gene deficiencies may act as risk modifiers for colorectal cancer risk, we investigated the relationship between genetic polymorphism in these genes and colorectal cancer risk in Egyptians. Sixty-six patients and 55 controls were included. Genotyping for GSTM1 and GSTT1 was conducted using PCR techniques and the results were related to epidemiologic and clinical information. No overall association was observed between GSTM1 or GSTT1 null genotypes and colorectal cancer risk. However, the data suggest a possible role for GSTM1 genotype in influencing tumor site. Furthermore, GSTM1 and GSTT1 genotypes, in conjunction with gender and place of residence, may play a role in modifying disease risk. Further studies on a larger population in Egypt are needed to generalize the results of this study.