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Sequential lymphoid neoplasms are rare and diagnostically challenging, with a variable clonal relationship. Here we present the case of a 59-year-old woman with mediastinal grey zone lymphoma (MGZL), who, shortly after achieving complete remission, developed a subsequent cutaneous neoplasm. Comparative molecular studies were performed using high-throughput sequencing (HTS), which demonstrated that both neoplasms shared high-allele-frequency EP300:p.P2333L and PTPRK:p.R532K variants. In addition, each neoplasm harboured private, mutually exclusive variants-NFKBIA:p.R245Sfs*39 and BTG2:c.142+5G>C in the MGZL and JAK1:p.Q562* and JAK1:p.G1097D in the skin. Integrating the clinical course with HTS, we diagnosed lymphomatoid papulosis and excluded relapse of the MGZL. Interestingly, the shared variants were likely germline rather than clonal, suggesting they created a permissive background predisposing to two independent transforming events along the B- and T-cell lineages. Molecular studies may help to reveal the genetic basis of composite lymphomas and to resolve diagnostically discordant, complex presentations.