Background: Optical coherence tomography (OCT) is a promising non-invasive imaging technique that has not systematically been studied in skin cancer such as basal cell carcinoma (BCC). Objective: We aimed, first, to describe the in vivo histologic features of BCC by using OCT, and second, to find out whether it is possible to differentiate BCC subtypes by means of OCT. Method. Prior to the excision, the BCCs (n = 43) as well as adjacent non-lesional skin sites we. e assessed by OCT in vivo. The lesional area of interest was marked prior to OCT and tattooed after excision, respectively, in order to enable topographical concordance between the cross-sectional OCT images and the histologic sections. Results: Compared to non-lesional skin, a toss of normal skin architecture and disarrangement of the epidermis and upper dermis was observed in the OCT images of BCCs. Features that were frequently identified by OCT and correlated with histology included Large plug-like signal-intense structures, honeycomb-like signal-free structures, and prominent signal free cavities in the upper dermis. With regard to the aforementioned OCT features, no statistically significant (P < 0.05) difference was found between nodular, multifocal superficial, and infiltrative BCCs, respectively. Conclusions: OCT is capable to visualize altered skin architecture and histopathological correlates of BCC. However, there is not at this time sufficient data supporting the clinical use of OCT for the differentiation of BCC subtypes. (c) 2006 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.