Systemic amyloidosis is a life-threatening disorder with a poor prognosis. Accurate and early diagnosis of the condition is of paramount importance as early initiation of therapy improves the prognosis and survival rate. A 49-year-old gentleman presented with recurrent right exudative pleural effusion. Thoracocentesis revealed unexplained exudative pleural effusion. Pleuroscopy and pleural biopsy showed chronic inflammatory changes with no atypical cells. Echocardiography revealed global dilated cardiomyopathy with an ejection fraction (EF) of 35%. He also had nephrotic range proteinuria of 2.83g/dL. A cystoscopy examination was performed due to macroscopic haematuria, and the bladder biopsy revealed focal acellular eosinophilic material within the stroma. Salmon red staining and apple-green birefringence were noticed under polarizing microscopy, suggestive of amyloidosis. Serum protein electrophoresis revealed raised alpha 1 globulin and alpha 2 globulins which support the diagnosis of primary systemic amyloidosis. Unfortunately, the patient passed away before the initiation of treatment due to cardiogenic shock. Early and less invasive tests for diagnosing systemic amyloidosis, such as abdominal fat pad aspiration and salivary gland biopsy, can be done. Given its systemic nature, early complications screening may benefit patients whereby targeted treatment can be given.