The United States Pharmacopeia (USP) General Chapters Expert Committee revised the General Information Chapter Near-Infrared Spectrophotometry <1119> in 2004 and introduced a USP Near Infrared (NIR) Calibrator Reference Standard (RS), which, in accordance with metrological principles was renamed the USP NIR System Suitability RS. The RS is intended for the qualification of NIR instrument wavelength uncertainty when measurements are taken in diffuse reflectance mode. The USP NIR System Suitability RS is a mixture of three rare earth oxides—dysprosium (Dy2O2), holmium (Ho2O3) and erbium (Er2O3)—plus talc [Mg3Si4O10(OH)2] in a 1: 1: 1: 1 ratio. This System Suitability RS was tested according to metrological principles based on International Organisation for Standardisation guidances during collaborative tests that established its suitability for use and reproducibility. This RS yields eight reference peaks that cover the spectral range between 1000 nm (10,000 cm−1) and 2500 nm (4000 cm−1) and are reported in an accompanying certificate. Analysts thus can use the USP NIR System Suitability RS for performance verification (i.e. to determine instrument wavelength uncertainty) when they operate NIR instruments in diffuse reflectance mode. This paper reviews the characteristics and metrologically informed development of the USP NIR system suitability RS for diffuse reflectance measurements and discusses the suitability of the RS for qualifying NIR instruments operating in the diffuse reflectance mode.