PURPOSE: Pain commonly occurs in cancer patients, and has been associated with shorter survival. However, the importance of pain is less clear when analyzed with other known prognostic variables. This systematic review was performed to better understand how pain impacts overall survival (OS) in common cancers when key clinical variables are included in multivariate analysis. METHODS: A Medline search was completed to find studies examining the relationship between pain, clinical variables, and OS in patients with breast, colorectal, lung, or prostate cancer. Multivariate analysis included known prognostic variables including age, performance status, disease burden, and laboratory parameters. RESULTS: Fifty studies met inclusion criteria. In patients with breast, colorectal, and lung cancer, pain was not a significant prognostic factor for OS on multivariate analysis in most studies. In contrast, several studies suggest that pain is an independent prognostic factor for OS in advanced prostate cancer, even when relevant clinical prognostic variables are included. However, analgesic use was often used as a surrogate for prostate cancer pain, making it difficult to determine whether pain or opioid exposure was more important in influencing survival. CONCLUSIONS: Pain may be associated with shorter survival in patients with cancer, but the mechanism for this relationship is unknown. The available evidence is insufficient to definitively determine if pain independently influences survival in patients with breast, colorectal, or lung cancer. The majority of studies in prostate cancer show pain to be an independent prognostic factor for OS, and often also incorporate opioid analgesic use in multivariate analysis. Prospective studies are needed to better understand how opioid utilization and pain may affect cancer progression and survival in diverse malignancies.