Objective This study analyzed the relationships between illness representations, psychological morbidity, family stress, and quality of life and whether these variables were mediated by body image and social support. Methods The sample consisted of 106 patients with skin tumors, who answered the following measures: Dermatology Life Quality Index, Illness Perception Questionnaire–Brief, Medical Outcomes Study Social Support Survey, Index of Family Relations, Hospital Anxiety and Depression Scales, and the Body Image Scale. Results Patients with poor quality of life showed more threatening cognitive and emotional illness representations, less perceived social support, higher psychological morbidity, and higher concern with body image. Body image mediated the relationship between cognitive and comprehension illness representations, family stress, psychological morbidity, and quality of life. Social support mediated the relationship between family stress/psychological morbidity and quality of life. Conclusions Psychological intervention should focus on body image and social support, particularly in patients with melanoma, less disease duration, tumors in the face, head or neck, in an active professional status, and with lower education.