OBJECTIVE: To identify the factors associated with difficulties encountered by nurses working in general wards in hospitals in Japan. METHODS: Questionnaires including items regarding difficulties in providing care to terminally ill cancer patients, the existence of a mentor regarding end-of-life issues, awareness of end-of-life issues, and demographic factors were administered to 375 staff nurses working in general in-patient wards. Multivariate regression analyses were employed to investigate correlations between factors. RESULTS: Multivariate regression analysis revealed that the existence of a mentor for end-of-life issues was associated with fewer difficulties in all areas other than "Knowledge and skill of nurses." Clinical experience was inversely related to difficulties in "Communication with patients and families" and "Personal issues." Greater awareness of end-of-life issues was related to higher difficulties in most areas. SIGNIFICANCE OF RESULTS: The existence of a mentor was correlated with fewer difficulties in most areas. Support by a palliative care team might be effective in reducing difficulties experienced by nurses and in improving care for terminally ill cancer patients. Basic communication training undertaken sooner after registration might be also useful.