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Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms with variable clinical behavior, ranging from indolent to aggressive. Immunohistochemical data regarding p16 and ß-catenin are conflicting, a direct comparative analysis of both makers has not been carried out and a correlation with the Demicco grading system is missing. A cohort of 30 surgically resected SFTs was analyzed by 11 immunohistochemical markers (p16, p53, Ki-67, PHH3, Cyclin E1, STAT6, ß-catenin, CD34, Vimentin, BCL2, CD99). Results (with a focus on p16 and ß-catenin) were statistically compared with the Demicco grading and available clinicopathological parameters. Three immunophenotypic subgroups were identified: p16+/ β-catenin- (12/30, 40%), p16-/ β-catenin+ (10/30, 33.3%) and double-negative (8/30, 26.7%); co-expression was not observed. The p16+ subtype showed higher Demicco scores, heterogeneous but often increased proliferative activity, frequent p53 alterations and the highest rate of metastases. In contrast, the β-catenin+ subtype occurred exclusively in pleuropulmonary SFTs and was associated with intermediate Demicco scores. Double-negative tumors clustered within the low-risk Demicco category and showed uniformly low proliferation indices. Overall, the three subtypes correlated significantly with Demicco risk classification (p = 0.0088). We identified three SFT subgroups based on p16 and β-catenin expression, which correlate with established Demicco risk categories and tumor localization. These markers may complement existing risk stratification and highlight biologically distinct subsets of SFT. Further studies are warranted to validate their clinical utility, particularly given their reproducibility and ease of implementation in routine diagnostic practice.