Objective: Vitreous opacity and cat contact history are two major diagnostic criteria for toxoplasmic retinochoroiditis. This study aimed to explore the causes of misdiagnosis and the clinical manifestations of patients with toxoplasmic retinochoroiditis who present with large yellowish-white necrotic retinal lesions but lack both a history of cat exposure history and vitreous opacity. Methods: This was a case series study. We collected clinical data from three patients diagnosed at Zhongshan Ophthalmic Center, Sun Yat-sen University between September 2021 and April 2023. All patients presented without a history of cat contact or vitreous opacity.The causes of misdiagnosis, clinical features, and treatment outcomes were analyzed. Results: The study included three patients (five eyes), all of them were female. One patient had no light perception in the contralateral eye after a 3-year disease course, while the other two exhibited bilateral involvement. The patients’ ages ranged from 31 to 34 years, and the duration of symptoms before diagnosis was 1–2 months. None reported exposure to cats, but all were immunocompromised: two had systemic lupus erythematosus (SLE) with irregular treatment and relapse, and one had underwent liver transplantation for "fulminant hepatic necrosis" and was receiving post-transplant immunosuppression. Fundus examination revealed no vitreous opacity, and retinal lesions appeared as large yellowish-white changes on fundus photography and necrotic changes on optical coherence tomography(OCT). Initially, all cases were misdiagnosed as acute retinal necrosis or cytomegalovirus retinitis, with 2 cases testing positive for herpesvirus DNA. Antiviral therapies were applied, which led to worsened vision and progression of the lesions. Subsequent referral testing of aqueous humor confirmed the presence of Toxoplasma gondii DNA. Anti-toxoplasma treatment resulted in significant resolution of the lesions and improvement in vision. Conclusions: In immunocompromised individuals, the presence of large necrotic retinal lesions without vitreous opacity or a history of cat exposure should raise suspicion for toxoplasmic retinochoroiditis. This awareness is crucial to prevent delayed diagnosis and subsequent vision loss.