The capability of optical coherence tomography (OCT) to perform “optical biopsy” of tissues within a depth range of with micron-scale resolution in real time makes it a promising biomedical imaging modality for dermatologic applications. Three high-speed, spectrometer-based frequency-domain OCT systems operating at (20,000 A-scans/s), , and (both 47,000 A-scans/s) at comparable signal-to-noise ratio (SNR), SNR roll-off with scanning depth, and transverse resolution were used to acquire 3-D tomograms of glabrous and hairy human skin in vivo. Images obtained using these three systems were compared in terms of penetration depth, resolution, and contrast. Normal as well as abnormal sites like moles and scar tissue were examined. In this preliminary study, skin pigmentation had little effect on penetration accomplished at three different wavelengths. The epidermis and dermal–epidermal junction could be properly delineated using OCT at , and this wavelength offered better contrast over the other two wavelength regions. OCT at permits imaging of deeper dermal layers, critical for detecting deeper tumor boundaries and other deeper skin pathologies. The performance at compromises between the other wavelengths in terms of penetration depth and image contrast.