Serum levels of soluble vascular cell adhesion molecule‐1 (sVCAM‐1, sCD106) were significantly elevated in patients with Hodgkin's disease (HD) (n = 101) compared to controls (n = 31) (P < 0.0001). sVCAM‐1 correlated with histology, stage, B‐symptoms, and prognostic markers (sICAM‐1, sCD30, sIL‐2R, LDH). sVCAM‐1, sICAM‐1 and sCD30 added independent prognostic information for both disease‐free and overall survival. 14 biopsies from 13 patients with HD were immunostained for VCAM‐1 and ICAM‐1. The vascular endothelium stained positive for VCAM‐1 in 10/12 evaluable biopsies and for ICAM‐1 in all evaluable biopsies. A stromal expression of both adhesion molecules precluded a precise evaluation of HRS‐cells. This led us to investigate VCAM‐1 (and ICAM‐1) expression in six Hodgkin cell lines (HDLM‐2, L428, L540, L591, DEV, KM‐H2). Two cell lines stained positive for VCAM‐1 (HDLM‐2, L591). All cell lines stained positive for ICAM‐1. sVCAM‐1 is a new prognostic marker in HD; its predictive power equals or surpasses that of sCD30 and sICAM‐1. Furthermore, two Hodgkin cell lines stained positive for VCAM‐1. This indicates that VCAM‐1 may be expressed by some HD tumour cells in vivo.