Renal dysfunction is often seen in patients with plasma cell dyscrasias. The abnormal light and heavy chains that are produced by the neoplastic plasma cells in these patients are responsible for the renal abnormalities that occur. The renal manifestations are heterogeneous and include alterations in all three renal compartments; sometimes more than one compartment is affected in a given case. It must be demonstrated that the renal abnormalities are directly related to the underlying plasma cell dyscrasia to make a definitive diagnosis of an associated lesion. Therefore, it becomes crucial to link the renal findings with the circulating nephrotoxic light or heavy chains. Immunofluorescence is very helpful and diagnostic in the majority of the cases, as it can localize the light or heavy chains to the various renal compartments showing alterations, and frequently confirm monoclonality. However, the antibodies that are used routinely do not necessarily label the abnormal light and heavy chains; the corollary of this is that a negative immunofluorescence workup does not rule out a light- or heavy-chain-related renal disorder. Electron microscopy is also important as it can depict crucial morphologic correlates to provide unique evidence or to simply confirm and clarify diagnostic findings. Ultrastructural immunolabeling combines the information obtained from immunofluorescence and electron microscopy by highlighting specific structures associated with the deposition of the pathogenic monotypical light and heavy chains.