Cardiac amyloidosis is an underrecognized cause of heart failure, particularly in patients with preserved ejection fraction (HFpEF). Its clinical presentation is often subtle and overlaps with more common cardiovascular conditions, leading to delayed or missed diagnosis. Primary care physicians may play a key role in early identification through recognition of characteristic clinical and laboratory “red flags”.To evaluate the prevalence of clinical and laboratory features suggestive of cardiac amyloidosis in a population followed in general practice and to assess the occurrence of confirmed diagnoses within this setting.A retrospective observational analysis was performed on 4,407 patients followed by general practitioners in L’Aquila and Avezzano (Italy) in May 2025. The presence of the following conditions was assessed: HFpEF, aortic stenosis, carpal tunnel syndrome, peripheral neuropathy, persistently elevated troponin levels, and ventricular hypertrophy.The mean age of the study population was 62.6 ± 8.4 years, and 54.9% were female. The most frequently observed conditions were left ventricular hypertrophy (4.15%), carpal tunnel syndrome (2.83%), persistently elevated troponin levels (2.06%), HFpEF (1.52%), peripheral neuropathy (0.42%), and aortic stenosis (0.03%). Two patients (0.03%) received a confirmed diagnosis of wild-type transthyretin cardiac amyloidosis.Although the prevalence of confirmed cardiac amyloidosis was low, multiple patients exhibited clinical features commonly associated with the disease. The coexistence of these findings in a primary care population highlights the potential for underdiagnosis and suggests that systematic evaluation of red flags may improve case detection outside specialized centers.Despite being classified as a rare disease, cardiac amyloidosis can be encountered in general practice. Increased awareness and recognition of suggestive clinical and laboratory features by general practitioners may facilitate earlier diagnosis and more timely referral, enabling access to disease-modifying therapies.