In addition to changes in facial morphology, head and neck cancer treatment can impact the facial expression. Quantification of changes in facial expression, particularly of smiling, would enable a deeper understanding of the relationship between physical changes and psychosocial adjustment in patients being treated for facial cancer. This study proposes 48 quantitative facial expression measures, which consist of the length normalized distances and slopes between 27 manually annotated fiducial points on standard 2D clinical photographs of patients with head and neck cancer. Using the proposed measures, the maximum intensity of smiling for patients with head and neck cancer prior to their treatments was compared to that of a sample from a healthy population. A total of 7 facial expression measures captured statistically significant differences between patients with head and neck cancer and healthy individuals. These measures suggest that patients with head and neck cancer are less expressive than people without head and neck cancer. This study is the first attempt to quantify the facial expression of patients with head and neck cancer and to build a foundation for studying how surgical interventions may affect their facial expressions. Moreover, this study lays the groundwork for future investigation of the relationship between facial expression and psychosocial adjustment in cancer patients.