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Perineural invasion (PNI) is a high-risk feature of cutaneous squamous cell carcinoma (CSCC). Depths at which PNI occurs are unknown.To determine the most superficial depth at which PNI occurs in CSCC and stratify by tumor clinical diameter and body location.Single-institution retrospective review of CSCC specimens reporting PNI on pathology reports between January 2004 and August 2014. Depth was defined as distance from top of granular layer to middle of nerve invaded by CSCC or distance from erosion to middle of nerve affected by CSCC.Of 66 specimens identified with PNI, 45 specimens were included. Mean histopathologic depth to PNI was 2.7 mm (SD = 1.8 mm, median depth = 2.2 mm, range 0.5–12 mm). Perineural invasion depth varied by anatomic location, with the head associated with most superficial average PNI depth (2.2 mm) and trunk with greatest average PNI depth (4.3 mm). Perineural invasion depth correlated with clinical tumor diameter. The largest percentage of specimens with PNI were of clinical diameter of at least 2 cm (20/45 = 44%).Clinicians encountering lesions suspicious for CSCC have the greatest chance of detecting PNI using biopsy techniques that reach at least 3 to 4 mm deep.