Skin cancer is the most common human malignancy, with basal cell carcinoma (BCC) the most frequent type. Aggressive forms of BCC are associated with extensive dermal invasion and destruction of collagen. Surgery is the most common treatment, but identification of tumor borders is a challenge. Polarization-sensitive optical coherence tomography (PS-OCT) is an optical method to examine collagen birefringence. To date, it has not been exploited for cancer management. As part of a pilot exploratory study to examine the use of OCT in skin cancer, we examined several tumors that pose a challenge to the surgeon due to their large size and histological subtype. In normal perilesional skin, OCT identifies epidermal and dermal structure; PS-OCT identified dermal birefringence. In BCC, tumors lost normal structure and gained the appearance of lobular impressions. PS-OCT identified an alteration of dermal birefringence. Examination of a border area revealed a gradual transition from more normal appearing image to frank tumor. These results indicate that PS-OCT can identify features that distinguish normal skin from tumor and may have the potential to guide surgeons in the treatment of aggressive skin cancer. © 2004 Society of Photo-Optical Instrumentation Engineers.