Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract, originating from structures differentiating towards Cajal cells. Due to their morphology and localization, the extragastrointestinal stromal tumors (EGISTs) can be a diagnostic challenge. We investigated a series of 51 EGISTs diagnosed in our institutions, aiming to explore the immunophenotypes and to analyze the process and the utility of the antibodies required for a positive diagnosis. Immunohistochemical examinations were done for pan-cytokeratin (pan-CK), Ki67, discovered on GIST1 (DOG1) protein and platelet-derived growth factor receptor alpha (PDGFRA), as necessary. The main tumor site was abdominal wall in 43 (84%) cases, most of the tumors showed spindle cell cellularity, followed by mixed and epithelioid type. Twenty-six cases revealed a full conventional immunohistochemical profile with DOG1 positivity. In 10 cases, c-KIT expression was absent but with the preservation of cluster of differentiation (CD)34 positivity, and eight cases were positive for PDGFRA. In our study, we found a subgroup of eight cases presenting in extra-abdominal settings (including one in lung and two in the head-and-neck area). We concluded EGISTs represent a histopathological and immunohistochemically challenging subgroup testing more often negative for c-KIT mutations and positive for PDGFRA compared to GIST. DOG1 remains the marker of choice regardless of tumor site, while CD34 and CD117 should be considered as adjuvants.