Comorbidities can have major implications for cancer care. They might impact the timing of cancer diagnosis, compromise optimal care, affect treatment outcomes and increase healthcare costs. Thus, it is important to infer the evidence about the prevalence of these comorbidities, explore variation between studies and examine trends over time.We performed a systematic literature review on the prevalence (and types) of comorbidities for the five most common forms of cancer. Additional inclusion criteria were: comorbidity based on routinely collected data, broad population, observational studies, publication between 1990 and June 25, 2020, published in English or Dutch, and from an OECD country. Multilevel analyses was performed to evaluate determinants for variation in comorbidity prevalence and trend over time.Our search yielded 3,070 articles of which 161 were eligible for data analyses. We found a weighted average comorbidity prevalence of 33.4%. Comorbidities are the most common in lung cancer (46.7%) and colorectal cancer (40.0%) followed by prostate (28.5%), melanoma (28.3%) and breast (22.4%). The most common types of comorbidities were hypertension (29.7%), pulmonary diseases (15.9%), and diabetes (13.5%). After adjusting for gender, type of comorbidities index, age, data source (patient records versus claims) and country, a significant increase in comorbidities of 0.54% per year was found.Given the large and increasing proportion of the oncological population that is dealing with comorbidities, it is important to explore optimal ways to incorporate comorbidity management in cancer care. However, there is large variation between studies and standardized registration and measurement tools for comorbidities are warranted.