Rationale: Cardiac transthyretin amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed because of the limited specificity of clinical manifestations, routine electrocardiogram, echocardiography and the traditional requirement for endomyocardial biopsy confirmation. Patient concerns: A 68-year-old female had suffered from lumbago for 5 years with progressive weakness, numbness in both lower limb. Diagnosis: The patient's clinical signs were not specific, but cardiac amyloidosis was suspected based on relative left ventricular apical sparing of longitudinal strain on echocardiography and continuous elevated serum levels of cardiac biomarkers (ultrasensitive cardiac troponin I and NT-proBNP). She was finally diagnosed hereditary transthyretin-related cardiac amylodosis by specific findings of cardiovascular magnetic resonance imaging (CMR), (99m)-technetium pyrophosphate (Tc-99m-PYP) scintigraphy and genetic testing. Interventions: The patient received medications including diuretics, beta-blockers and angiotensin-converting enzyme inhibitors at the time of hospitalization. Ultimately, however, she refused further treatments and requested discharge from our hospital. Outcomes: A series of noninvasive technique enables the diagnosis of hereditary transthyretin-related cardiac amyloidosis. Lessons: While endomyocardial biopsy is not able to performed, this case demonstrates that a combination of noninvasive techniques, especially CMR, nuclear imaging, and genetic testing, may help us to make a correct diagnosis of hereditary transthyretin-related cardiac amyloidosis.