Background: Cutaneous squamous cell carcinoma is the second most common malignancy of the skin, often occurring in older patients and in the head and neck area (cSCCHN). Age, life expectancy, and frailty are not taken into consideration by current guidelines. Objectives: The objective of this study was to evaluate the influence of frailty and life expectancy on guideline deviation, treatment outcomes, and quality of life (QoL) after treatment in patients with cSCCHN. Methods: Patients with cSCCHN were prospectively included. A geriatric assessment was performed, including the Geriatric 8 (G8), Groningen Frailty Indicator, and Timed Up and Go test (TUG). The Lee index was used to predict a limited life expectancy, and the Adult Comorbidity Evaluation-27 was used as a comorbidity index. QoL was assessed by the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire at three time points. Results: Seventy-seven patients with cSCCHN were included. Frail patients had significantly more high-risk tumours. Guideline deviation occurred in 7.8% and was more common in patients who were frail (G8), with high-risk tumours (>= T2), with a limited life expectancy or an increased TUG. Guideline deviation did not lead more often to progression of disease in our study. No predictors for post-operative complications were found. BaSQoL subscores were very low at each time point and did not change significantly with time in the total group. Frail patients reported more fear of recurrence or new tumours 3 months after treatment, and less concern about other people's skin 6 months after treatment, compared to non-frail patients. Complication rate, gender, or guideline deviation did not affect any subscale scores. Conclusions: Assessment of frailty and life expectancy can guide physicians and patients in treatment decisions. Deviation from guidelines towards less aggressive treatment schedules can be considered in frail patients with a limited life expectancy, since it did not negatively affect short-term outcomes or QoL in patients with cSCCHN in our study. However, these results should be confirmed by other, larger prospective studies with a longer follow-up period.