Optical coherence tomography (OCT) is an optical technique that measures the backscattering of near-infrared light by tissue. OCT yields in 2D and 3D images at micrometer-scale resolution, thus providing optical biopsies, approaching the resolution of histopathological imaging. The technique has shown to allow in vivo differentiation between benign and malignant epithelial tissue, through qualitative assessment of OCT images, as well as by quantitative evaluation, e.g., functional OCT. This study aims to summarize the principles of OCT and to discuss the current literature on the diagnostic value of OCT in the diagnosis of epithelial (pre)malignant lesions. The authors did a systematic search of the electronic databases PubMed and Embase on OCT in the diagnostic process of (pre)malignant epithelial lesions. OCT is able to differentiate between benign and (pre)malignant lesions of epithelial origin in a wide variety of tissues. In this way, OCT can detect skin cancers, oral, laryngeal, and esophageal cancer as well as genital and bladder cancer. OCT is an innovative technique which enables an optical biopsy of epithelial lesions. The incorporation of OCT in specific tools, like handheld and catheter-based probes, will further improve the implementation of this technology in daily clinical practice.