Simple SummaryThere is a drive to detect cancers at an early stage to improve survival. While this initiative has been associated with better outcomes for certain cancers, testing also leads to patient anxiety and distress. Most of the research in this domain was conducted in asymptomatic patients who attend as part of population-based testing (screening). The literature in individuals with symptoms or with abnormal preliminary results (diagnostics) remains deficient. We conducted a literature search to identify which cancers were underrepresented, what risk factors could contribute to worse psychological outcomes in both screening and diagnostics, and whether any interventions could help to mitigate these. Our search revealed that young, unemployed individuals were at high risk and should therefore be targeted for support. Among the interventions considered, the use of patient leaflets, one-stop clinics, and patient navigators to facilitate patient attendance at their appointments appeared to be the most beneficial.Abstract(1) Background: Several studies have described the psychological harms of testing for cancer. However, most were conducted in asymptomatic subjects and in cancers with a well-established screening programme. We sought to establish cancers in which the literature is deficient, and identify variables associated with psychological morbidity and interventions to mitigate their effect. (2) Methods: Electronic bibliographic databases were searched up to December 2020. We included quantitative studies reporting on variables associated with psychological morbidity associated with cancer testing and primary studies describing interventions to mitigate these. (3) Results: Twenty-six studies described individual, testing-related, and organisational variables. Thirteen randomised controlled trials on interventions were included, and these were categorised into five groups, namely the use of information aids, music therapy, the use of real-time videos, patient navigators and one-stop clinics, and pharmacological or homeopathic therapies. (4) Conclusions: The contribution of some factors to anxiety in cancer testing and their specificity of effect remains inconclusive and warrants further research in homogenous populations and testing contexts. Targeting young, unemployed patients with low levels of educational attainment may offer a means to mitigate anxiety. A limited body of research suggests that one-stop clinics and patient navigators may be beneficial in patients attending for diagnostic cancer testing.