OBJECTIVES: The objective of this study was to describe the prevalence of microscopic pancreatic, hepatic and renal lesions in post-mortem samples from Cavalier King Charles spaniels. METHODS: The prevalence of microscopic lesions was determined by routine histopathology and compared to ante-mortem clinical signs. RESULTS: There was evidence of chronic pancreatitis in 51·9% of the cases, and age correlated with severity. Renal lesions were diagnosed in 52·2% of cases, most of which were inflammatory. Ante-mortem diagnosis of pancreatic and renal disease was 25 and 16·7%, respectively. Primary hepatic lesions were diagnosed in 11·1% of cases; secondary hepatic lesions were diagnosed in 64·8%. CLINICAL SIGNIFICANCE: Pancreatic and renal lesions are common in Cavalier King Charles spaniels, but they have similar rates of hepatic disease as the general population. The increasing prevalence of pancreatic lesions with age suggests that it might be a progressive condition.