There is increasing use of HR-OCT for the diagnosis and monitoring of clinical and subclinical OSSN lesions. Topical pharmacotherapy agents, including interferon α-2b, 5-fluorouracil, and mitomycin C, have demonstrable efficacy in the treatment of OSSN and their use may be dictated based upon tumor factors, patient factors, cost, and side effect profile. Both surgical excision and adjunctive topical medications have excellent success, with the favored treatment method trending towards topical pharmacotherapy as primary therapy.