Background/Objectives: Epstein–Barr virus (EBV) detection patterns in lymphoproliferative disorders (LPDs) show significant geographical variation worldwide. Regional epidemiological data are essential for understanding viral distribution patterns and developing appropriate clinical surveillance strategies. This study aimed to determine EBV detection frequency in LPDs using available molecular and immunohistochemical methods in Western Mexico. Methods: We conducted a cross-sectional study of 200 formalin-fixed paraffin-embedded tissue samples from patients diagnosed with LPDs (2015–2019) at Hospital Civil de Guadalajara. EBV detection combined with real-time PCR targeting the BNTp143 gene and immunohistochemistry for LMP-1 protein. Cases were classified following current WHO criteria. Statistical analysis included multivariate logistic regression, diagnostic concordance assessment, and age-stratified analysis. Results: EBV detection frequency reached 35.5% overall, with marked differences between neoplastic (53.9%) and reactive LPDs (24.2%) (OR: 3.515; 95% CI: 1.859–6.645, p < 0.001). Hodgkin lymphoma showed the highest detection rate (80.6%), significantly exceeding non-Hodgkin lymphoma (39.3%) (OR: 6.43; 95% CI: 2.08–19.41, p = 0.001). Age-stratified analysis revealed predominant adult involvement (49.1% vs. 22.0% in young adults, p = 0.025). We identified three epidemiological categories based on detection probability patterns. Conclusions: This study represents the first comprehensive molecular and immunohistochemical characterization of Epstein–Barr virus in lymphoproliferative disorders from Western Mexico, establishing distinct epidemiological patterns that align with Latin American regional characteristics. The validated methodology provides a reproducible framework for multi-center studies, while the epidemiological data serve as an essential baseline for future longitudinal research and resource optimization in similar healthcare settings.