No robust biomarkers have been yet validated to identify the recurrence of disease in classical Hodgkin Lymphoma (cHL) patients upon induction treatment. The relevance of the inflammatory microenvironment in cHL prompted us to investigate the key immunomodulator myeloid dendritic cells type-1 (mDC1), type-2 (mDC2) and plasmacytoid dendritic cells (pDC). Blood DC levels were assessed in 52 newly diagnosed patients through multiparametric flow-cytometry. All but two patients received ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine). The median counts of all DC subsets were lower in cHL patients than in healthy controls (P < 0·001). Median mDC counts were inferior for the advanced vs early stage patients for both mDC1s and mDC2s (P = 0·008; P = 0·0007 respectively). Also, median mDC2 counts were reduced in case of bulky (P = 0·0004) and extra-nodal (P = 0·046) disease. Patients with B symptoms had lower levels for mDC1s (P = 0·046), mDC2s (P = 0·009) and pDCs (P = 0·040). All the DC subtypes increased at the end of treatment in 26 patients (P < 0·001): 4·6-fold for mDC1, 2·4-fold for mDC2, 4·5-fold for pDC and aligned DCs subsets with the reference frequencies and the interquartile ranges of the controls. In conclusion, DCs may contribute to the disturbed immunological interplay typical of cHL, prompting a further evaluation of their value as a potential new biomarker.