BACKGROUND: Missed opportunities for diagnosing cancer cause patients harm and have been attributed to suboptimal use of tests and referral pathways in primary care. Primary care physician (PCP) factors have been suggested to affect decisions to investigate cancer, but their influence is poorly understood. OBJECTIVE: To synthesise evidence evaluating the influence of PCP factors on decisions to investigate symptoms of possible cancer. METHODS: We searched MEDLINE, Embase, Scopus, CINAHL and PsycINFO between January 1990 and March 2021 for relevant citations. Studies examining the effect or perceptions and experiences of PCP factors on use of tests and referrals for symptomatic patients with any cancer were included. PCP factors comprised personal characteristics and attributes of physicians in clinical practice. DATA EXTRACTION AND SYNTHESIS: Critical appraisal and data extraction were undertaken independently by two authors. Due to study heterogeneity, data could not be statistically pooled. We, therefore, performed a narrative synthesis. RESULTS: 29 studies were included. Most studies were conducted in European countries. A total of 11 PCP factors were identified comprising modifiable and non-modifiable factors. Clinical judgement of symptoms as suspicious or 'alarm' prompted more investigations than non-alarm symptoms. 'Gut feeling' predicted a subsequent cancer diagnosis and was perceived to facilitate decisions to investigate non-specific symptoms as PCP experience increased. Female PCPs investigated cancer more than male PCPs. The effect of PCP age and years of experience on testing and referral decisions was inconclusive. CONCLUSIONS: PCP interpretation of symptoms as higher risk facilitated testing and referral decisions for possible cancer. However, in the absence of 'alarm' symptoms or 'gut feeling', PCPs may not investigate cancer. PCPs require strategies for identifying patients with non-alarm and non-specific symptoms who need testing or referral. PROSPERO REGISTRATION NUMBER: CRD420191560515.