Survival and quality of life in head and neck cancer are directly linked to the size of the primary tumor at first detection. In order to achieve substantial gain at these issues, both, primary prevention and secondary prevention, which is early detection of malignant lesions at a small size, have to be improved. So far, there is not only a lack in the necessary infrastructure not only in Germany, but rather worldwide, but additionally the techniques developed so far for early detection have a significance and specificity too low as to warrant safe implementation for screening programs. However, the advancements recently achieved in endoscopy and in quantitative analysis of hypocellular specimens open new perspectives for secondary prevention. Chromoendoscopy and narrow band imaging (NBI) pinpoint suspicious lesions more easily, confocal endomicroscopy and optical coherence tomography obtain optical sections through those lesions, and hyperspectral imaging classifies lesions according to characteristic spectral signatures. These techniques therefore obtain optical biopsies. Once a “bloody” biopsy has been taken, the plethora of parameters that can be quantified objectively has been increased and could be the basis for an objective and quantitative classification of epithelial lesions (multiparametric cytometry, quantitative histology). Finally, cytomics and proteomics approaches, and lab-on-the-chip technology might help to identify patients at high-risk. Sensitivity and specificity of these approaches have to be validated, yet, and some techniques have to be adapted for the specific conditions for early detection of head and neck cancer. On this background it has to be stated that it is still a long way to go until a population based screening for head and neck cancer is available. The recent results of screening for cancer of the prostate and breast highlight the difficulties implemented in such a task.