Hyperkeratotic lesions on the palms and soles are one of the most frequent clinical presentations encountered in dermatological practice, with a myriad of underlying etiologies that closely resemble one another and are clinically indistinguishable. Histopathological examination is the tool used by dermatologists to arrive at a final diagnosis, but it is invasive and not feasible under all circumstances. Dermoscopy is a new age, increasingly popular, noninvasive diagnostic technique of great value that is used to diagnose underlying etiology by acting as a bridge between clinical and histopathological pictures. This study aimed to evaluate the various etiologies underlying palmoplantar hyperkeratosis and the role of dermoscopy in the diagnosis of each disease along with its ability to delineate a close differential diagnosis and ensure appropriate treatment. Materials and methodsThis was a hospital-based observational cross-sectional study conducted from July 1 to December 31, 2022. Consenting patients with hyperkeratotic palmoplantar lesions on clinical examination attending the dermatology outpatient department at our tertiary care hospital were included after institutional ethical clearance was obtained. Patients with HIV, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) infection, or a history of hyperkeratotic lesions since birth, i.e., inherited palmoplantar keratodermas, were excluded from the study. A total of 60 patients aged between 18 and 60 years who met the above criteria were included. A complete history was taken; a thorough examination was performed. Routine investigations and tissue histology were done. Potassium hydroxide (KOH) mount and patch testing were done as and when required. Dermoscopy with DermLite DL4 was performed in all cases on lesional areas, and the findings were noted.