Background: Systemic lupus erythematosus (SLE) is a multi-systemic heterogeneous autoimmune disease. Attempts have been made trying to classify lupus into more homogenous subsets with pathogenic, therapeutic, or prognostic significance. Objective: was to evaluate the possibility of existence of the main clinical features of Systemic Lupus Erythematosus (SLE) in clusters. Patients and Methods: The demographic data, cumulative clinical and laboratory features of 150 Egyptian SLE patients were studied. Some of the main clinical manifestations were then selected for cluster analysis using the K-means cluster analysis procedure. Results: Three distinct groups of patients were identified. Cluster 1 (n: 27) showed higher age at diagnosis and was characterized by high prevalence of mucocutaneous manifestations (malar rash, discoid rash, photosensitivity, oral ulcer) and arthritis but having low prevalence of serositis and hematologic manifestations (hemolytic anemia, leukopenia, and thrombocytopenia). Patients in cluster 2 (n: 81) showed mainly renal and hematological manifestations but had the lowest prevalence of mucocutaneous manifestations and arthritis. Cluster 3 patients (n: 42) had the most heterogeneous features; they had a high prevalence of mucocutaneous manifestations, serositis, hematologic manifestations and renal involvement. Conclusion: patients with systemic lupus erythematosus could be divided into clusters of distinct patterns of clinical manifestations.