Background: Unused medications (UM) are an important issue, with the waste associated with UM a burden to the health-care system. The aims of this study were to clarify the amount and costs of UM in patients with advanced cancer at the time of their last admission to a palliative care unit and to explore the factors contributing to the cost of UM and how patients dealt with UM. Methods: A prospective observational study was conducted in single palliative care unit. Unused medications were classified into 6 categories and the number and cost of UM by category calculated per patient. Patients were classified into 2 cost groups (high and low) based on the total cost of UM, and the number and cost of UM by category were compared between these 2 groups. Results: Of 194 consecutive hospitalized patients, data were analyzed for 90. The mean number and cost of UM per patient was 440 and US$301, respectively. Opioids accounted for 47% of the cost of UM. Comparing costs by UM category, the proportion of opioids (51% vs 21%; P < .0001) and oral anticancer drugs (14% vs 3%; P = .02) was higher in the high- than in the low-cost group. Conclusion: Based on the results of the present study, the estimated annual waste cost of UM for patients with cancer who died in Japan was approximately US$110 million. Interventions to educate patients regarding UM and to eliminate barriers to opioid use may help reduce the cost of UM, particularly opioids and anticancer drugs.