Introduction: Nowadays clinicians don't have a useful tumoral marker to perform the follow up of patients affected of head and neck cancers (H&NC). Objectives: To analyse the operative characteristics of prealbumin (PRB) as a tumoral activity marker in those affected of head and neck cancer compared with albumin, total proteins, carcinoembryonic antigen, and alfa fetoprotein. Methods: It was performed an observational prospective study with patients visited in Hospital Universitari Arnau de Vilanova de Lleida (Spain) with the main diagnosis of H&NC. During study time main epidemiological, clinical, and analytical (including PRB) characteristics were collected in 3 times: at diagnosis, after finishing the treatment and 12 months later. Results: Blood samples were obtained from 138 patients from the 1st January 2007 till the 1st February 2010. Median age was 62.5 (29-89) years and 121 (88%) were males. Most frequent histological diagnosis was scamous carcinoma 87 cases (63%). 19 patients (14.5) died during that time. Sensitivity, specificity, positive and negative predictive values of PRB were 63%, 100%, 100%, 87% respectively. The area under receiver operating characteristic curve was 0.87 (CI 0.76-0.98), that was better than other parameters studied. Conclusions: Prealbumin is a useful tumoral activity marker in those affected of head and neck cancer and it could be a useful tool in these patients follow up.