Indolent and aggressive non-Hodgkin lymphomas (NHL) are common types of hematologic malignancies but their effect on quality of life (QoL) is understudied. In particular, the relation between different aspects of QoL and cognitive impairments and coping styles is relevant for individualized physical and mental health care. We studied emotional, physical, and subjective well-being in relation to cognitive capacities and coping style in 100 patients with NHL (44 females, age 61.3 ± 13.6). Questionnaires assessed health-related QoL (Functional Assessment of Cancer Therapy (FACT)), affect (Hospital Anxiety and Depression Scale, Positive and Negative Affective Schedule), distress (Distress Thermometer), and locus of control; semi-structured interviews targeted subjective QoL (Schedule for Evaluating the Individual Quality of Life) and cognitive impairments (Test for Early Detection of Dementia with Differentiation from Depression). Indolent NHL (n = 44) yielded better health-related QOL and positive affect and less anxiety than the aggressive type (n = 55; FACT: t(97) = 1.90, p = .028, anxiety: t(97) = −1.9, p = .030; positive affect: t(96) = 2.01, p = .023). In a factor analysis, physical and affective scales loaded on an emotional and physical well-being factor, which differed between the groups. Further, cognitive capacities and locus of control contributed to subjective QoL and reported distress. Emotional and physical scales assess QoL in NHL. However, The behavioral psychobiology group of the RWTH Aachen University seeks to unravel systemic biological factors underlying and influencing human well-being. The principal method is functional imaging in addition to psychometric approaches. Psychosomatic effects on emotions and cognitions are studied as well as regulation strategies to improve well-being using behavioral, pharmacological, and neurofeedback approaches.