OBJECTIVE To evaluate the strength of evidence supporting a possible association between salmon calcitonin (SCT) use and cancer incidence. METHODS Searches of MEDLINE/PubMed, MEDLINE/OVID, and EMBASE (January 1973 to September 2013) were performed using the key search terms salmon calcitonin, humans, nasal calcitonin, and (for EMBASE only) randomized controlled trial. We also performed a manual review of data reviewed by the US Food and Drug Administration (FDA) committee in 2013. METHODS All articles identified from the data sources were evaluated and all information deemed relevant was included for this review. RESULTS Intranasal and injectable SCT are FDA-approved for the treatment of postmenopausal osteoporosis. After a safety signal suggested a possible link between SCT use and prostate cancer, the European Medicines Agency and FDA regulatory agencies conducted analyses of SCT randomized controlled trial data to assess cancer-related adverse events and to readdress the approval status of SCT. Eighteen studies were found that compared nasal or oral SCT and placebo. In 15 of the 18 studies, the percentage of malignancy was greater in the SCT arm. The studies varied in quality, outcomes, and length. Most of the studies had poor-quality methods to assess new cancer cases. CONCLUSIONS Current evidence may suggest an association between SCT use and cancer incidence based on studies with poor-quality cancer assessment methods. However, considering the lack of demonstrated efficacy of SCT to reduce fractures, clinicians should consider discontinuing its use for osteoporosis treatment regardless of the FDA's final approval decision.