Introduction: Syphilis, a systemic, sexually transmitted inflammatory disease caused by Treponema pallidum, presents challenges in diagnosis due to its varied manifestations. Ocular syphilis often presents with non-specific symptoms. This study aims to elucidate the diagnostic process through the analysis of two patient cases, including one with HIV co-infection. Material and Methods: The study evaluated two ocular syphilis cases, diagnosed using comprehensive treponemal (fluorescent treponemal antibody absorption test, Treponema pallidum hemagglutination assay, enzyme immunoassay) and nontreponemal (venereal disease research laboratory test, rapid plasma reagin test) testing. Factors such asuveitis symptoms, sexual behavior, drug use, previous treatments, and available medical history were considered. Results: The results highlight the complexity of ocular syphilis diagnosis. Both cases underscored the need to include ocular syphilis in differential diagnoses for eye infections or inflammations, especially in patients with high-risk behaviors, drug use, or a history of syphilis. The non-specific nature of symptoms necessitates comprehensive testing for accurate diagnosis. Conclusions: This study reinforces the importance of considering ocular syphilis in the differential diagnosis of inflammatory eye diseases. A meticulous approach combining both treponemal and nontreponemal tests is crucial for accurate diagnosis. These findings emphasize the need for thorough clinical evaluation and history-taking in patients presenting with ocular symptoms.