Our epidemiological and genetic analyses of sporadic and familial retinoblastoma indicate that an X-chromosome-linked gene is involved in the genesis of a significant fraction of new bilateral cases of the disease. The activity of this gene results in sex-ratio distortion in favor of males among patients with bilateral sporadic disease. Among the offspring of these males, both sex-ratio distortion in favor of males and transmission-ratio distortion in favor of affecteds are observed. We propose that these phenomena are due to the inability of these males to erase the genome imprint established on the half of the genome inherited from their mothers.