Purpose: We looked for any predictive value of change in primary tumor and metastatic lymph node volumes after induction chemotherapy (IC) on oncologic outcome in head and neck squamous cell carcinoma (HNSCC). Methods: Nineteen patients with stage IVA/B HNSCC treated between 2004 and 2010 with at least one cycle of IC (docetaxel, cisplatin and 5-fluorouracil / TPF) and concomitant chemoradiotherapy (CRT) with cisplatin were retrospectively analyzed. Volumes were calculated separately for primary tumor (Vtm), lymph node metastases (Vln) and their sum (Vsum) on computed tomography (CT) images before and after IC. The effect of volumetric changes on locoregional failure (LRF), distant metastasis (DM) and overall survival (OS) was assessed. P values <0.05 were considered as statistically significant. Results: The median follow-up of surviving patients was 25 months (range: 10.7-83.3). The median number of cycles and duration of TPF was 3 (range: 1-4) and 44 days (range: 4-116), respectively. Empirical area under the curve (AUC) analyses for death, LRF and DM revealed optimal cut-off values of Vtm diminution (30.54%, AUC: 87%) and Vsum decrease (35.45%, AUC: 64.55%) only for OS (p <0.05). Among those, a reduction in Vsum more than 35.4% between pre- and post-IC was significantly correlated with better OS (100 vs 43% at 2 years, p <0.05). Conclusion: Volumetric shrinkage of the tumor load after IC assessed with CT seems to predict OS. The assessment of volumetric shrinkage upon IC might be used to decide whether to offer patients alternative strategies like palliative/de-intensified treatments or more aggressive combined modalities after IC.