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Background Cryptococcal lateral flow antigen assays (CLFAs) have been assessed in comparison to the latex cryptococcal antigen agglutination test but their clinical performance is unknown. Objective Determine clinical performance of IMMY CLFA (Immuno‐Mycologics Inc, Oklahoma) using patients with and without cryptococcosis as the reference standard. Animals One‐hundred ninety‐seven serum samples from client‐owned dogs and cats. Methods Review of medical records of a referral population of dogs and cats that had CLFA performed between 2012 and 2020. Animals were classified as cryptococcosis positive (Cr+) or negative (Cr−) based on clinical information. Clinical diagnosis was used to calculate positive and negative percent agreement of the CLFA. Results Twelve specimens (4 canine, 8 feline) were obtained from Cr+ animals and had positive CLFA results. One‐hundred eighty‐five specimens (139 canine, 46 feline) were collected from Cr− animals. Negative CLFA results were recorded in 129 canine and 44 feline Cr− samples. Positive CLFA results were noted for 10 canine and 2 feline Cr− samples. Positive percent agreement of CLFA was 100% (confidence interval [CI], 39.8%‐100% dogs; 63.1%‐100% cats). Negative percent agreements were 92.8% (CI, 87.2%‐96.5%) for dogs and 95.7% (CI, 85.2%‐99.5%) for cats. Conclusions and Clinical Importance A negative IMMY CLFA result enables reliable exclusion of cryptococcal infection in dogs and cats. By contrast, a positive result must be interpreted cautiously and further testing should be performed to verify a diagnosis of cryptococcosis.