Background: Complexity has become a core issue in caring for patients with advanced disease and/or at the end-of-life. The Hexagon of Complexity (HexCom) is a complexity assessment model in the process of validation in health-care settings. Our objective is to use the instrument to describe differences in complexity across disease groups in specific home care for advanced disease and/or at the end-of-life patients, both in general and as relates to each domain and subdomain. Methods: Cross-sectional study of home care was conducted in Catalonia. The instrument includes 6 domains of needs (clinical, psychological/emotional, social/family, spiritual, ethical, and death-related), 4 domains of resources (intrapersonal, interpersonal, transpersonal, and practical), and 3 levels of complexity (High (H), Moderate (M), and Low (L)). Interdisciplinary home care teams assessed and agreed on the level of complexity for each patient. Results: Forty-three teams participated (74.1% of those invited). A total of 832 patients were assessed, 61.4% of which were cancer patients. Moderate complexity was observed in 385 (47.0%) cases and high complexity in 347 (42.4%). The median complexity score was 51 for cancer patients and 23 for patients with dementia (p<0.001). We observed the highest level of complexity in the social/family domain. Patients/families most frequently used interpersonal resources (80.5%). Conclusions: This study sheds light on the high-intensity work of support teams, the importance of the social/family domain and planning the place of death, substantial differences in needs and resources across disease groups, and the importance of relationship wellbeing at the end-of-life.