Background: Practice-pattern data, evidence-based knowledge and transfer, and performance management strategies define Cancer Care Ontario’s quality improvement strategy. Knowledge products, such as practice guidelines, are intended to provide recommendations for practice, based on best available evidence, to improve quality of care and reduce variation in practice. Review of 2010-2011 Cancer System Quality Index (CSQI) data revealed complex practice patterns in treatment of non-small cell lung cancer patients with stages II and IIIa resected and stages IIIa and IIIb non-resected disease in Ontario. A multi-method study was initiated to understand the patterns, to identify if a quality of care problem exists and to propose improvements moving forward. Methods: Surgeons, medical oncologists and radiation oncologists from Ontario were invited to participate in a survey consisting of 6 areas of inquiry. A grounded theory approach was used to guide key informant interviews of purposively sampled clinicians and administrators. A more in-depth analysis of the CSQI data was planned. Results: Clinicians responding to survey provided positive assessments of PG recommendations and evidentiary base; perceptions of practice patterns were less problematic than hypothesized; estimates of benchmarks were highly variable; and assessments of barriers to recommendation implementation included slow referral process, lack of organization support and patients seen in practice not reflected in the evidence. From the interviews, 5 themes emerged: unique patient, unique physician, family, clinical team, and clinical evidence. Further analysis of CSQI data was not possible given limitations related to data collection. Conclusions: A perceived quality of care problem initiated this study. Concerns centred on significant proportion of patients receiving no treatment; modest percentage of patients receiving treatment that aligned with PG recommendations; and regional variation within each of the clinical care options. Our data show that defining a quality of care problem is significantly more complex than consideration of practice patterns alone.