Background. Treatment of early cancer stages is deeply connected to a good prognosis, a moderate reduction of the quality oflife, and comparably low treatment costs. Methods. Head and neck squamous cell carcinomas were investigated using the multimodal combination of coherent anti-Stokes Raman scattering(CARS), two-photon excited fluorescence (TPEF), and secondharmonic generation (SHG) microscopy.Results. An increased median TPEF to CARS contrast was found comparingcancerous and healthy squamous epithelium with a p value of 1.8_10210. A following comprehensive image analysis was able to predict the diagnosis of imaged tissue sections with an overall accuracy of90% for a 4-class model.Conclusion. Nonlinear multimodal imaging is verified objectively as a valuable diagnostic tool that complements conventional staining protocols and can serve as filter in future clinical routine reducing the pathologist’sworkload.