Nuclear retinoid receptors mediate retinoid effects in controlling cell growth, differentiation, apoptosis, and carcinogenesis. Altered expression or activity of these receptors could abolish the retinoid signal transduction pathway and be associated with human carcinogenesis. In situ hybridization is a powerful tool for analyzing gene expression in formalin-fixed, paraffin-embedded tissue sections, especially for newly cloned genes or when no antibodies are available. Detection of altered retinoid receptor expression using in situ hybridization in premalignant and malignant tissues has provided important information about the roles of these receptors in cancer development and the response of these tissues to retinoid treatment. Among these receptors, altered expression of retinoic acid receptor-beta (RAR-beta) has been mostly detected in human cancers, including those of the head and neck, lung, esophagus, mammary gland, pancreas, and cervix. RAR-beta is thus currently used as a surrogate endpoint biomarker in different clinical prevention trials of various cancers.