Background Studies on stigmatization of cancer patients show a moderate or high relevance of perceived stigmatization. To date, there are no studies with explicit focus on stigma in relation to oncological therapy. We investigated the role of oncological therapy on perceived stigma in a large sample. Methods Quantitative data from 770 patients (47,4% women; 88%≥50 years) with breast, colorectal, lung, or prostate cancer were analyzed as part of a registry-based bicentric study. Stigma was assessed with the German version of the SIS-D; the validated instrument includes four subscales in addition to a total score. Data were analyzed using the t-test and multiple regression with various sociodemographic and medical predictors. Results Of the 770 cancer patients, 367 (47,7%) received chemotherapy, possibly in combination with other therapy (surgery, radiotherapy). All stigma scales showed significant mean differences (effect sizes up to d=0,49) with higher scores for patients receiving chemotherapy. The multiple regression analyses of the respective SIS-scales demonstrate a significant influence of the variables age (β≤- 0,266) and depressivity (β≤0,627) on perceived stigma in all five models, and (in four models) a significant influence of the variable chemotherapy (β≤0,140). Radiotherapy shows only a weak influence in all models and surgery has no relevance. The explained variance ranges from R2=27 to 46,5%. Discussion and Conclusion The findings support the assumption of an association of oncological therapy, especially chemotherapy, on the perceived stigmatization of cancer patients. Relevant predictors are depression and younger (<50) age. These (vulnerable) groups should therefore receive special attention and psycho-oncological care in clinical practice. Further research on the course and mechanisms of therapy-related stigmatization is also necessary.