Ionizing radiation affects the metabolism of key proteins of extracellular matrix including type III collagen, an important component of human skin. The aim of the work is an analysis of the impact of radical and palliative radiotherapy on collagen type III synthesis in patients with head and neck cancer. The test group consisted of 56 males with histopathologically confirmed head and neck cancer, for whom radiotherapy was applied as a form of radical or palliative treatment. The level of procollagen III aminoterminal propeptide (PIIINP), which is a marker of collagen type III synthesis, was determined in blood serum before radiotherapy, immediately following radiotherapy, and 3 months after it was finished. As a result of radical radiotherapy a statistically significant decrease of PIIINP levels in serum (p < 0.0001) was observed, both immediately after the radiotherapy and 3 months after the end of the treatment. Also the palliative radiotherapy caused a significant decrease of PIIINP right after the treatment (p = 0.0052), as well as during the examination performed 3 months later (p = 0.0004). The achieved results suggest that PIIINP can be used as a marker helpful in assessing radiation damage to connective tissue.