A 47-year-old African American man with a medical history significant for hypertension, type 2 diabetes, and gastroesophageal reflux disease was given atorvastatin at 40 mg daily for a markedly elevated low-density lipoprotein-cholesterol (LDL-C) of 279 mg/dL (millimoles per liter, multiply by 0.0259). He was subsequently tried on various statins, but owing to hip pain thought possibly because of these agents, a rise in liver enzymes, and persistently elevated LDL-C, he was referred to the Boston Medical Center Lipid Clinic Fasting lipid profile in December 2013 on no lipid-lowering agents included an LDL-C level of 232 mg/dL. He restarted atorvastatin at 40 mg daily because it was determined that his hip pain was more likely because of arthritis than statin therapy. The adherence and effectiveness of lipid-lowering therapy were then routinely monitored by measuring direct LDL-C levels, which dropped to 113 mg/dL in June 2014 and 115 mg/dL in October 2015, respectively. Interestingly, his directly measured LDL was 115 mg/dL in October 2015, but a calculated LDL-C was 170 mg/dL in December 2015. Repeat fasting lipid profiles with simultaneously calculated and directly measured LDL-C levels, apolipoprotein B (Apo B), and lipoprotein (a) (Lp[a]) were subsequently assessed in April 2016 and June 2016. They confirmed a marked difference between the direct LDL-C level and calculated LDL-C levels (Table).