Updated project metadata. Approximately 800,000 leukaemia and lymphoma cases are diagnosed worldwide each year. Burkitt’s lymphoma and chronic lymphocytic leukaemia represent contrasting examples of B-cell cancers, modelled by Eμ-myc and Eμ-TCL1 mice, respectively. To better understand B-cell cancers and systemic effects of oncogenesis, tumours and plasma from these models were profiled by mass spectrometry proteomics. 8270 cellular and 2095 plasma proteins were fully quantitated by isobaric labelling, of which 695 and 279 demonstrated overabundance coinciding in both tumour models, respectively. Co-occurring upregulated cellular tumour processes included ribosome biogenesis, translation, cell cycle promotion and chromosome segregation. Tumour plasma overabundance highlighted immunity, inflammation, microenvironment interactions, a prolific tumour lysis signature and putative biomarkers of early-stage cancer. Integrative evaluation of tumours and plasma provided systemic insight not captured in isolation. Overall, these findings provide a detailed characterisation of systemic oncogenesis in two contrasting B-cell tumour models, identifying extensive common profiles in both tumour cells and plasma.