Adrenocortical carcinoma (ACC) is a highly aggressive endocrine malignancy originating from the adrenal cortex, among which the undifferentiated subtype is rare and associated with a high risk of clinical misdiagnosis. Here we report a case of ACC with concurrent RET gene fusion and undifferentiated pathological features. The patient presented without classic clinical manifestations of ACC and tested negative for canonical adrenocortical immunohistochemical markers. The definitive diagnosis was established based on biopsy and surgical histopathology, endocrine function assessment, systemic imaging, molecular pathological testing using next-generation sequencing, and multidisciplinary team consultation. This study highlights the value of an integrated diagnostic strategy for the identification and differential diagnosis of rare ACC subtypes and suggests that RET may serve as a potential therapeutic target. In addition, through a review of the relevant literature, this study summarizes the molecular-pathological characteristics of ACC carrying genetic variants, aiming to improve clinicians' understanding of the diagnosis and management of rare ACC subtypes.

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