Background: Cutaneous T-cell lymphoma (CTCL) negatively impacts quality of life (QoL), but existing QoL questionnaires may not comprehensively reflect patients’ experience. Objectives: To identify the aspects of QoL that are most meaningful to patients with CTCL and to evaluate existing QoL instruments in this context. Methods: Semistructured interviews were conducted between May and June 2019 using purposive sampling of patients with CTCL. Data were analysed by an inductive thematic approach using Dedoose Version 8.0.35. Results: One-on-one interviews lasting a median of 43 min were completed by 18 patients [median age 62 years (interquartile range 52–70); 39% advanced-stage (IIB–IV)]. Itch was the most common clinical symptom reported (16 of 18 patients), followed by pain (12 of 18), skin breaks (11 of 18) and skin flaking (10 of 18). Eleven patients reported that their symptoms interfered with sleep, which impacted daily functioning. Patients also noted a lack of understanding of the disease in the community and felt uncertain (12 of 18), depressed (11 of 18), suicidal (four of 18) and hopeless (nine of 18). Nearly all patients (17 of 18) reported a sense of ‘otherness’ (not feeling ‘normal’ or ‘like themselves’), and most patients (16 of 18) specifically mentioned concern about their physical appearance. Patients also noted substantial treatment burden. Salient patient concerns, including individual clinical symptoms, concern about appearance and problems with sleep, were not adequately or consistently represented in generic, skin-specific or CTCL-specific QoL measures. Conclusions: Incorporating the concerns and priorities that distinguish patients with CTCL from other patient populations will be of paramount importance in developing a comprehensive CTCL-specific measure of QoL that adequately captures patients’ experience.