Radiation therapy uses high-energy rays (such as x-rays) and particles (such as photons, electrons, or protons) to kill cancer cells. External beam radiation therapy focuses radiation from outside the body on the skin tumor.

If a tumor is very large or is located on an area of the skin that makes surgery difficult, radiation may be used as the primary (main) treatment instead of surgery. Primary radiation therapy is often useful for some elderly patients who, because of poor general health, cannot tolerate surgery. Radiation therapy can cure small non-melanoma skin cancers and can delay the growth of more advanced cancers. Radiation is also useful in combination with other therapies. It is particularly useful for Merkel cell carcinoma.

In some cases, radiation can be used after surgery as adjuvant (additional) therapy to kill any small deposits of remaining cancer cells that may not have been visible during surgery. This lowers the risk of cancer coming back after surgery. Radiation may also be used to help treat non-melanoma skin cancer that has spread to lymph nodes or other organs.

Side effects of radiation include skin irritation, redness, and drying. With longer treatments, these side effects may get worse. After many years, new skin cancers sometimes arise in areas previously treated by radiation. For this reason, radiation usually is not used to treat skin cancer in young people. Radiation is also not recommended for people with certain inherited conditions (such as basal cell nevus syndrome) because they may be more at risk to the cancer-causing effect of radiation.