Standard of care diagnostic procedure for suspected skin cancer is microscopic examination of hematoxylin & eosin stained tissue by a pathologist. Areas of high inter-pathologist discordance and rising biopsy rates necessitate higher efficiency and diagnostic reproducibility. We present and validate a deep learning system which classifies digitized dermatopathology slides into 4 categories. The system is developed using 5,070 images from a single lab, and tested on an uncurated set of 13,537 images from 3 test labs, using whole slide scanners manufactured by 3 different vendors. The system's use of deep-learning-based confidence scoring as a criterion to consider the result as accurate yields an accuracy of up to 98%, and makes it adoptable in a real-world setting. Without confidence scoring, the system achieved an accuracy of 78%. We anticipate that our deep learning system will serve as a foundation enabling faster diagnosis of skin cancer, identification of cases for specialist review, and targeted diagnostic classifications.Every year in the United States, 12 million skin lesions are biopsied 1 , with over 5 million new skin cancer cases diagnosed 2 . After a skin lesion is biopsied, the tissue is fixed, embedded, sectioned, and stained with hematoxylin and eosin (H&E) on glass slides, ultimately to be examined under microscope by a dermatologist, general pathologist or dermatopathologist who provides a diagnosis for each tissue specimen. Owing to the large variety of over 500 distinct skin pathologies 3 and the severe consequences of a critical misdiagnosis 4 , diagnosis in dermatopathology demands specialized training and education. Although the inter-observer concordance rate in dermatopathology is estimated to be between 90 and 95% 5,6 , there are some distinctions which present frequent disagreement among pathologists, such as in the case of melanoma vs. melanocytic nevi 7-11 . Any system which could improve diagnostic accuracy provides obvious benefits for dermatopathology labs and patients; however, there are substantial benefits also to improving the distribution of pathologists' workloads 12-14 . This can reduce diagnostic turnaround times in several scenarios. For example, when skin biopsies are interpreted initially by a dermatologist or a general pathologist, prior to referral to a dermatopathologist, it can result in a delay of days, sometimes in critical cases. In another common scenario, additional staining is required to identify characteristics of the tissue not captured by standard H&E staining. If those additional stains are not ordered early enough, there can be further delays to diagnosis. An intelligent system to distribute pathology workloads could alleviate some of these bottlenecks in lab workflows. The rise in adoption of digital pathology 1,15 provides an opportunity for the use of deep learning-based methods for closing these gaps in diagnostic reliability and efficiency 16,17 .