Multicentric reticulohistiocytosis (MRH) is a rare, class IIb non-Langerhans cell histiocytosis associated with skin and joint involvement. It is more prevalent (80%) in Caucasian females in their fifth to sixth decade of life. Patients usually demonstrate symptoms and signs of symmetric polyarthritis and papulonodular cutaneous lesions. In addition to skin and joints, multiple organs can be involved, such as the lung (pleural effusion, interstitial fibrosis, hilar lymphadenopathy), heart (pericardial effusion, myocarditis), gastrointestinal system, and urogenital system (genital tract and kidney). Pericardial involvement is a rare manifestation, and around three cases have been reported in the literature so far. Our case report is a valuable contribution to the literature, which aids clinicians in contemplating MRH as one of the differentials among patients presenting with pericardial effusion. We described the characteristics of MRH along with its differentiating features from other autoimmune conditions and management.