We report the result of the follow-up molecular analysis of a bronchial carcinoma in situ treated by 13-cis-retinoic acid, which relapsed 9 months after cessation of drug therapy. Loss of heterozygosity at 3p21 and 9p22 genomic sequences were assessed by polymerase chain reaction (PCR) after microdissection of the dysplastic epithelia. Despite a transient regression of the lesion to a lower grade with treatment, molecular analysis showed the persistence of a 3p and 9p deletion in all the bronchial biopsies taken in the same area during a 1 year follow-up, preceding by 9 months the recurrence of the carcinoma in situ. Our findings suggest that molecular follow-up analysis can help to assess the persistence of a malignant clone within a bronchial epithelium that displays a more benign phenotype under retinoid treatment on follow-up. Molecular analysis may be of great importance to evaluate the effects of chemoprevention and to determine the duration of such intervention in responder patients.