Background: Diagnostic imaging may be a major source of distress in patients with advanced cancer, a condition known as “scanxiety”. Scanxiety represents a complex array of negative and stressful emotions linked with cancer scans, and the uncertainties and fears that may accompany them. We aimed to evaluate the prevalence and characterize risk factors for scanxiety among cancer patients and their caregivers and evaluate the impact of scanxiety on quality of life (QoL), during the COVID-era. Methods: We conducted a cross-sectional survey study of metastatic cancer patients treated at the University Hospital of Larisa and their caregivers. Eligible patients met the following inclusion criteria: age > 18 years old, ability to speak and write fluently in Greek, having had at least one imaging study during the period of the study (seven days before the survey), approval of the patient’s oncologist to approach the patient. Patients/caregivers with pre-existing (prior to cancer diagnosis anxiety disorder) were excluded from the study. After completion of the informed consent process, patients/caregivers completed all survey items. We used a modified version of the Greek version of the Impact of Event Scale-Revised (IES-R-Gr) to specifically assess distress associated with scans, and QoL was measured using the EORTC QLQ-C30 questionnaire. Results: 218 patients with metastatic cancer and their caregivers were included in the study. Patient's mean age was 66 years (range 35-88). The majority were men (61%) and were diagnosed with Non-Small-Cell Lung Cancer. 71% had an IES-R-Gr score that was suggestive of scanxiety. Their symptoms were more severe symptoms while waiting for the results. Patients with a recent diagnosis (< 6 months) had higher levels. Interestingly, 16% of the patients had postponed a check-up due to scanxiety, while 77% reported that stress does not decrease over time. The majority of caregivers (81%) reported scanxiety, without a strong correlation with the score of the respective patients. Unlike patients, the majority of caregivers reported an increase in stress during the COVID-19 period. The presence of scanxiety was associated with decreased QoL in patients (p = 0.004). Conclusions: Scanxiety is a common problem among patients with metastatic cancer and is associated with impaired QoL. To our knowledge this is the first study implying that caregivers also experience scanxiety and may be a persistent problem.