Background: Sézary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL), defined by erythroderma, lymphadenopathy and circulating malignant T lymphocytes with cerebriform nuclei (Sézary cells). Its non-specific skin presentation often delays diagnosis. Case Presentation: A 55-year-old man with no relevant medical history presented with a generalized pruritic erythroderma evolving over several weeks, with asthenia and intermittent fever. Examination revealed cervical and axillary lymphadenopathy and mild splenomegaly (2 cm below the costal margin). Diagnostic Findings: The blood count showed moderate leukocytosis (12.77 G/L) without anemia (hemoglobin 12.8 g/dL) or thrombocytopenia (platelets 290 G/L). The May-Grünwald-Giemsa-stained blood smear showed 53% small-to-medium lymphoid cells with grooved, cerebriform nuclei. Whole-blood flow cytometry identified an abnormal T-cell population representing 84% of lymphocytes, with strong CD45, a CD3+/CD4+/CD7−/CD56− phenotype and a CD4/CD8 ratio >10. Conclusions: The association of erythroderma, characteristic Sézary cell morphology and an aberrant CD4+/CD7− phenotype allowed rapid diagnosis of SS. Combined blood smear review and flow cytometry are rapid, minimally invasive and decisive tools in the work-up of unexplained erythroderma.