Because cancer pain can in many cases be intermittent, the presence or absence of pain in ambulatory care patients on any given clinic visit may not be an accurate characterization of the impact of pain on functioning or health-related quality of life (HRQOL). The purpose of this study was to describe the relationship between temporal aspects of pain presentation and HRQOL among 187 stage III/IV cancer patients using the Brief Pain Inventory and the EORTC QLQ-C30. A total of 43% of patients reported pain the previous week, with 22% reporting no pain at the time of assessment. Differences between three pain groups (No Pain, Past Pain, and Current Pain) were significant for global HRQOL and five dimensions of HRQOL. Severity of pain was also associated with each dimension of HRQOL. This study highlights the complex relationship between pain presentation and HRQOL. The findings support the continuing need for detailed pain assessments among cancer patients treated in ambulatory care settings. Specifically, standardized, self-report measures of cancer pain that include ‘frequency’ as well as severity may be the most accurate approach to capture the impact of pain on HRQOL.