Objective Because cancer‐related stigmatization is prevalent but difficult to change, research on its impact on psychological burden and respective intervening variables is needed. Therefore, we investigated the effect of stigmatization on depressive symptomatology and whether body image mediates this relationship. Methods This bicentric study assessed patients of 4 major tumor entities. We measured stigmatization (SIS‐D), depressive symptomatology (PHQ‐9), and body image (FKB‐20). Applying multiple mediator analyses, we calculated the total effect of stigmatization on depressive symptomatology and the indirect effects exerted via the 2 body image scales rejecting body evaluation and vital body dynamics. Results Among the 858 cancer patients recruited (breast: n = 297; prostate: n = 268; colorectal: n = 168; lung: n = 125), stigmatization showed total effects on depressive symptomatology across all stigma dimensions (all ptotal sample < .001). Except for lung cancer patients, this result was replicated for each cancer group. Body image as a whole was shown to mediate the effect across all samples (γtotal sample = .04, 95%‐CI: 0.03‐0.06). Among the total sample and prostate cancer patients, the mediating effect of rejecting body evaluation was significantly larger than the effect of vital body dynamics (dtotal sample = .02, 95%‐CI: 0.01‐0.04). Conclusions Perceived stigmatization is an important and generalizable risk factor for depressive symptomatology among cancer patients. Apart from interventions addressing stigmatization, improving body image could additionally help to reduce the psychological burden in stigmatized patients.