Monoclonal gammopathies can cause renal tubular epithelial damage through multiple mechanisms, the most common manifestation being myeloma cast nephropathy. Amyloid light chain amyloidosis rarely affects the renal tubular epithelium directly and usually causes glomerular injury. Amyloid deposition can also be seen within vessel walls and in the renal tubulointerstitium. Herein, we describe a unique pattern of κ light chain amyloid deposition involving the proximal tubule epithelium in a patient with multiple myeloma, characterized by intracellular amyloid globule formation with concomitant phenotypic changes suggestive of histiocytic differentiation of tubular epithelial cells. Amyloid pathogenesis is thought to be closely associated with the reticuloendothelial system, more specifically macrophages, and histiocytic differentiation of mesangial cells seems to be an integral step in glomerulopathic amyloid production. Our report proposes a similar mechanism of amyloidogenesis in the renal tubular epithelium.