Melamine, a nitrogen-rich chemical, was implicated in pet and human food recalls in 2007, which caused enormous economic losses to the food industry. In this study, melamine concentration in wheat gluten, chicken feed, and processed foods (that is, cake and noodle) was measured by surface enhanced Raman spectroscopy (SERS) in combination with SERS-active substrates. SERS was able to rapidly detect 0.1% melamine in wheat gluten, 0.05% in chicken feed, 0.05% in cakes, and 0.07% in noodle, respectively. A partial least squares (PLS) model was established for the quantification of melamine in foods by SERS: R= 0.90, RMSEP = 0.33. In addition, SERS results were verified by HPLC analysis based on a simplified FDA method. Compared with HPLC, the SERS method is much faster and simpler, requires minimum sample preparation, but still yields satisfactory qualitative and quantitative results. These results demonstrate that it is an applicable approach to use SERS to screen foods, eliminate presumptive negative samples of melamine contamination from the sample population, and then verify presumptive positive samples using HPLC protocols. Combining these 2 methods could provide a more rapid and cost-effective way for monitoring melamine contamination in increasingly large numbers of imported foods and feed products.