Purpose: To provide practice guidelines for delineating clinical target volume (CTV) for radiotherapy planning of non melanoma (NMSC) skin cancers. Methods and materials: A prospective, single arm, study. Preoperatively, a radiation oncologist outlined the boundary of a gross lesion, and drew 5-mm incremental marks in four directions from the delineated border. Under local anesthesia, the lesion was excised, and resection margins were assessed microscopically by frozen section. Once resection margins were clear, the microscopic tumor extent was calculated using the presurgical incremental markings as references. A potential relationship between the distance of microscopic tumor extension and other variables was analyzed. Results: A total of 159 lesions in 150 consecutive patients, selected for surgical excision with frozen section assisted assessment of resection margins, were accrued. The distance of microscopic tumor extension beyond a gross lesion varied from 1 mm to 15 mm, with a mean of 5.3 mm. The microscopic tumor extent was positively correlated with the size of gross lesion, histology and number of surgical attempts required to obtain a clear margin. To provide a 95% or greater chance of covering microscopic disease we make the following recommendations for CTV margins; 10 mm for BCC less than 2 cm, 13 mm for BCC greater than 2 cm, 11 mm for SCC less than 2 cm, and 14 mm for SCC greater than 2 cm. Conclusions: Tumors greater than 2 cm and SCC histology required larger margins to adequately cover the microscopic extent of disease. This information is crucial in radiation planning of NMSC. Clinicians should be cautioned, as these guidelines may not offer optimum treatment for patients with extremely large or small lesions.