Scleroderma is an autoimmune disease characterized by the progressive and dysregulated accumulation of collagen in the skin and internal organs. Pulmonary complications including interstitial lung disease have emerged as the greatest cause of mortality in this disease. Because treatments are limited, new areas of investigation are sorely needed. An emerging area of interest in this field is a potential role for fibrocytes as biomarkers or mediators of disease. Fibrocytes are monocyte-derived mesenchymal progenitor cells that exhibit features of extracellular matrix production and wound contraction in addition to immunologic functions such as cytokine and chemokine production, antigen presentation, leukocyte trafficking, and modulation of angiogenesis. Fibrocytes could participate in the pathogenesis of scleroderma lung disease through any or all of these functions and may be useful biomarkers of disease activity. This chapter presents protocols that have been developed for the study of fibrocytes obtained from human circulation and tissues. Protocols for the quantification of fibrocytes in murine models also are described, along with discussion of common technical challenges. It is hoped that this information will allow further investigation of the role that fibrocytes might play in Scleroderma-related lung disease and perhaps lead to new areas of study in this difficult-to-treat and deadly disease.