Abstract In a prospective study, a large number of patients with basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) underwent surgery using three dimensional (3D) histology and were evaluated with respect to local recurrence. The excised tumours were treated using 3D-histology with a routine paraffin procedure until the surgical margins were clear of tumour. Prospective evaluation of recurrence-free survival and overall survival of 5227 primary BCCs in 3320 patients and 615 invasive primary SCCs in 600 patients was conducted in the form of a letter-based follow-up with feedback from the patients and the referring physicians. The mean follow-up period was 5 years. In the BCC collective, 36 out of 3320 patients developed local recurrence (1%, calculated as a percentage of treated BCCs: 0.7%). In the SCC collective, 20 local recurrences appeared (3%). The recurrence rate for SCCs with desmoplasia was 24%, whilst the recurrence rate for common types of SCC without desmoplasia was 1%. Surgery followed by 3D histology results in very low recurrence rates for BCC and SCC with no additional effort compared with the normal histopathological procedure.