The purpose of this study is to develop hyperspectral imaging (HSI) for automatic detection of head and neck cancer cells on histologic slides. A compact hyperspectral microscopic system is developed in this study. Histologic slides from 15 patients with squamous cell carcinoma (SCC) of the larynx and hypopharynx are imaged with the system. The proposed nuclei segmentation method based on principle component analysis (PCA) can extract most nuclei in the hyperspectral image without extracting other sub-cellular components. Both spectra-based support vector machine (SVM) and patch-based convolutional neural network (CNN) are used for nuclei classification. CNNs were trained with both hyperspectral images and pseudo RGB images of extracted nuclei, in order to evaluate the usefulness of extra information provided by hyperspectral imaging. The average accuracy of spectra-based SVM classification is 68%. The average AUC and average accuracy of the HSI patch-based CNN classification is 0.94 and 82.4%, respectively. The hyperspectral microscopic imaging and classification methods provide an automatic tool to aid pathologists in detecting SCC on histologic slides.