Diagnostic algorithm in symptomatic patients. Ideally, AL amyloidosis should be diagnosed at a presymptomatic stage. When amyloidosis is suspected, the first step should be searching for a monoclonal protein with sensitive technology. Patients with suspect cardiac involvement in whom monoclonal components are not detected may undergo a biopsy-free diagnostic process.⁵⁸ Scintigraphy with bone-seeking tracers, such as DPD, PYP, and HMDP, can diagnose ATTR amyloidosis without a biopsy in the absence of a plasma cell dyscrasia, but cardiac uptake can be seen also in patients with AL amyloidosis. In the presence of a monoclonal component biopsy-based diagnosis and typing with mass spectrometry,¹⁰² or, in highly specialized laboratories, with immunohistochemistry or immuno-electron microscopy¹⁰² are mandatory. Amyloid deposits can be demonstrated with minimally invasive procedures, such as biopsy of abdominal fat, bone marrow, and minor salivary glands. Abdominal fat aspirate has excellent feasibility and good sensitivity (∼85% when associated with bone marrow biopsy) in AL amyloidosis.¹⁰³ If less invasive biopsies are negative, a biopsy of an affected organ will typically be required. Genetic testing allows discrimination between hereditary and wild-type TTR amyloidosis and identification of rarer hereditary variants. *In patients with a monoclonal protein, amyloid deposits should be searched also in the bone marrow biopsy. DPD, scintigraphy with ^99mTc 3,3-diphosphono1,2-propanodicarboxylic acid; FLC, circulating free light chains; HMDP, scintigraphy with ^99mTc-hydroxymethylene diphosphonate; PYP, scintigraphy with ^99mTc-pyrophosphate; SIFE, serum immunofixation electrophoresis; UIFE, urine immunofixation electrophoresis.