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Knowledge of breed associations is valuable to clinicians and researchers investigating diseases with a genetic basis.Among symptomatic dogs tested for exocrine pancreatic insufficiency (EPI) by canine trypsin-like immunoreactivity (cTLI) assay, EPI is common in certain breeds and rare in others. Some breeds may be overrepresented or underrepresented in the population of dogs with EPI. Pathogenesis of EPI may be different among breeds.Client-owned dogs with clinical signs, tested for EPI by radioimmunoassay of serum cTLI, were used.In this retrospective study, results of 13,069 cTLI assays were reviewed.An association with EPI was found in Chows, Cavalier King Charles Spaniels (CKCS), Rough-Coated Collies (RCC), and German Shepherd Dogs (GSD) (all P.001). Chows (median, 16 months) were younger at diagnosis than CKCS (median, 72 months, P.001), but not significantly different from GSD (median, 36 months, P = .10) or RCC (median, 36 months, P = .16). GSD (P.001) and RCC (P = .015) were younger at diagnosis than CKCS. Boxers (P.001), Golden Retrievers (P.001), Labrador Retrievers (P.001), Rottweilers (P = .022), and Weimaraners (P = .002) were underrepresented in the population with EPI.An association with EPI in Chows has not previously been reported. In breeds with early-onset EPI, immune-mediated mechanisms are possible or the disease may be congenital. When EPI manifests later, as in CKCS, pathogenesis is likely different (eg, secondary to chronic pancreatitis). Underrepresentation of certain breeds among dogs with EPI has not previously been recognized and may imply the existence of breed-specific mechanisms that protect pancreatic tissue from injury.