Purpose <p>hTERT messenger RNA (hTERT mRNA) has been detected in peripheral blood of different cancer patients and its elevation seems related to clinicopathological parameters and treatment efficacy. The objectives are analyzing if hTERT mRNA levels are increased in cancer patients, detecting it they change after treatment and determining if they could be useful in disease monitoring.</p> Methods <p>A prospective, analytical, case-control study was conducted, in which peripheral blood of 37 head and neck squamous cell cancer patients and 30 healthy donors were obtained. hTERT mRNA expression levels were determined by PCR-RT. Follow-up of cancer patients was carried out during one year with blood extractions at 7 days for surgical patients, and 1, 2, 6 and 12 months after finishing treatment for all patients.</p> Results <p>hTERT mRNA expression levels were elevated in plasma of cancer patients (0,75) compared to controls (0,5) (<i>p</i> = 0.003). Patients in more advanced stages had higher hTERT mRNA levels (<i>p</i> = 0.008). hTERT mRNA levels during follow-up did not change significantly at the different time points but showed a tendency to decrease, comparing treatment responders with tumour persistence patients. An early decrease of hTERT mRNA levels was observed in the five cured patients who underwent surgery.</p> Conclusions <p>Detection of plasma hTERT mRNA after surgery might help to identify patients with better prognosis. Quantitation of plasma hTERT mRNA could be a complementary tool for diagnosis, but still further studies are needed to clarify the role and causes of variable circulating hTERT mRNA levels for prognosis and follow-up.</p>