Aim. This paper is a report of a study of the inter-observer reliability of the European Pressure Ulcer Advisory Panel pressure ulcer classification system and of the differential diagnosis between moisture lesions and pressure ulcers. Background. Pressure ulcer classification is a valuable tool to provide a common description of ulcer severity for the purposes of clinical practice, audit and research. Despite everyday use of the European Pressure Ulcer Advisory Panel system, its reliability has been evaluated in only a limited number of studies. Methods. A survey was carried out between September 2005 and February 2006 with a convenience sample of 1452 nurses from five European countries. Respondents classified 20 validated photographs as normal skin, blanchable erythema, pressure ulcers (four grades), moisture lesion or combined lesion. The nurses were familiar with the use of the European Pressure Ulcer Advisory Panel classification scale. Results. Pressure ulcers were often classified erroneously (kappa = 0.33) and only a minority of nurses reached a substantial level of agreement. Grade 3 lesions were regularly classified as grade 2. Non-blanchable erythema was frequently assessed incorrectly as blanchable erythema. Furthermore, the differential diagnosis between moisture lesions and pressure ulcers appeared to be complicated. Conclusion. Inter-observer reliability of the European Pressure Ulcer Advisory Panel classification system was low. Evaluation thus needs to focus on both the clarity and complexity of the system. Definitions and unambiguous descriptions of pressure ulcer grades and the distinction between moisture lesions will probably enhance clarity. To simplify the current classification system, a reduction in the number of grades is suggested.