A small molecule pharmaceutical company received multiple field complaints describing the presence of yellow discoloration observed on a commercially marketed, white, film-coated tablet. This report describes the investigation to identify the root cause and the subsequent corrective action. The yellow discoloration was connected to the presence of sulfasalazine, a compound not found in use or inventory within the company manufacturing facility. Experimentation demonstrated that sulfasalazine interacts with polyethylene glycol 1450, the plasticizer in the tablet film coating. Tablets that contacted sulfasalazine residue on pharmacy counting trays at the time of pharmacy dispensing developed yellow spots and streaks that were the cause of product complaints. Alternative film coating plasticizers were evaluated. An acceptable alternate coating was identified, scaled-up, approved by FDA, and ultimately used in commercial product. Complaints of yellow discoloration were completely eliminated after implementation of the revised coating. This case study illustrates two unexpected occurrences: 1) Inactive ingredients in a formulation are not always inert and may be reactive, and 2) Problems may be caused by sources completely unrelated to the product ingredients, manufacturing process, product storage, or other causes associated with the manufacturing site. Compliance personnel must keep an open mind without preconceived beliefs when investigating problem situations, and must be sufficiently flexible to allow for changes in direction as based upon the results of investigations. [ABSTRACT FROM AUTHOR]