Background: Hodgkin lymphoma (HL) is one of the most frequent cancers occurring at a young age. Although diagnosis of HL is not difficult, a minimally invasive method to diagnose HL, and a radiationfree method to confirm the remission status are highly desired. Methods: In this study, we employed cutting-edge Luminex technology to evaluate 67 soluble plasma proteins for their suitability for diagnosis and for confirming remission of classical HL (cHL). Results: Soluble cluster of differentiation (CD)30 and CC motif chemokine ligand (CCL)22 were identified to be capable of differentiating cHL patients from healthy donors and from patients with diffuse large B cell lymphoma (DLBCL), a disease that shares many characteristics with cHL. Soluble tumor necrosis factor receptor (TNFR)2 was found to be lower in the remission than in the initial diagnosis cohort of cHL patients, and also to be lower in plasmas at remission than in plasmas at initial diagnosis from the same patients. In DLBCL plasmas, concentrations of interleukin (IL)-2, soluble IL-2 receptor and IL-31 changed in patients upon entering remission. Conclusions: Measurement of these factors may: 1) provide a minimally-invasive method to diagnose and differentiate HL and DLBCL, and 2) make it possible to monitor the remission status of these patients without use of radiation-based imaging.