INTRODUCTION: There are no validated patient-reported outcome (PRO) instruments for Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV+ PTLD). The aim of this study was to assess the content applicability for three frequently used PRO instruments from the perspective of patients with EBV+ PTLD. METHODS: A moderated focus group comprising adult patients with EBV+ PTLD was conducted using a concept confirmation and an open-ended concept elicitation approach. The domains of the EuroQoL Group-5 Dimension (EQ-5D) instrument, Short Form Health Survey-Version 2 (SF-36v2) questionnaire, and Functional Assessment of Chronic Illness Therapy-Lymphoma (FACT-LYM) questionnaire were discussed. The concept elicitation portion was a general discussion of symptoms and patient burden of EBV+ PTLD. RESULTS: Six patients participated in this study: five women and one man. Most participants reported acute pain in the location of their EBV+ PTLD. All participants reported significant physical fatigue and experienced productivity loss. Patients reported emotional fatigue, feelings of dissociation, lack of motivation, and persistent fear of disease progression, including mortality. Patients described their social functioning as disjointed, behaving differently with loved ones/caregivers than when alone. The EQ-5D was relevant for the pain/discomfort and anxiety/depression domains; most SF-36v2 domains were relevant, with the exception of the general health perception domain, which was not applicable; all domains in the FACT-LYM were relevant. The open-ended portion drew no new content. CONCLUSIONS: This qualitative research identified meaningful concepts in patients with EBV+ PTLD, with physical, emotional, and social functioning being impacted. The FACT-LYM questionnaire was the most relevant of the three PROs studied, with all domains relevant to this population. It is important to properly analyze PRO data in patients with EBV+ PTLD.